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At least 109 records · Page 6Linked to original sources
PubMed1983

Eradication of tumor cells after injection into immunized hosts compared with the eradication of tumor cells after transfer of immune peritoneal exudates into tumor-bearing recipients.

DBA/2 mice were immunized against the syngeneic SL2 lymphoma by two or five injections with irradiated lymphoma cells given IP or SC, respectively. The antitumor efficacy induced in immunized mice was tested by (a) IP injection of the immunized mice with nonirradiated tumor cells and (b) transfer of the total 'immune' peritoneal exudate, the cellular fraction only, or the cell-free fraction only, IP into tumor-bearing recipients, or (c) tumor neutralization tests (Winn assay). It was shown that immunized mice were able to reject 5 X 10(7) SL2 tumor cells (8 of 14 mice survived greater than 100 days), while in most transfer experiments 2 X 10(5) SL2 cells could be eradicated. In the tumor neutralization experiments a number of 10(6) SL2 cells were eradicated. When the immune exudates were given before the inoculations of SL2 tumor cells the number of survivors increased significantly. Further, it was shown that the cellular fraction is the major contributor to the antitumor effect in the transfer experiments, since there was no significant difference in tumor eradication after injection of a complete immune exudate and after injection of the isolated cellular fraction. Injection of the noncellular fraction had no measurable antitumor effect. An increase in the number of injections with total peritoneal exudates from immunized mice did not result in an increase in tumor eradication in the tumor-bearing recipients. Extra stimulation (IP) of immunized mice with 10(4) nonirradiated cells 6 days after the last immunization resulted in an increase of the antitumor efficacy of these peritoneal exudates of these mice when collected 4-24 h after this stimulation. Extra stimulation with 10(6) irradiated cells had no measurable effect.

Animals↗
PubMed2002

IP(3)-mediated Ca(2+) signals in human neuroblastoma SH-SY5Y cells with exogenous overexpression of type 3 IP(3) receptor.

Human neuroblastoma SH-SY5Y cells, predominantly expressing type 1 inositol 1,4,5-trisphosphate (IP(3)) receptor (IP(3)R), were stably transfected with IP(3)R type 3 (IP(3)R3) cDNA. Immunocytochemistry experiments showed a homogeneous cytoplasmic distribution of type 3 IP(3)Rs in transfected and selected high expression cloned cells. Using confocal Ca(2+) imaging, carbachol (CCh)-induced Ca(2+) release signals were studied. Low CCh concentrations (< or = 750 nM) evoked baseline Ca(2+) oscillations. Transfected cells displayed a higher CCh responsiveness than control or cloned cells. Ca(2+) responses varied between fast, large Ca(2+) spikes and slow, small Ca(2+) humps, while in the clone only Ca(2+) humps were observed. Ca(2+) humps in the transfected cells were associated with a high expression level of IP(3)R3. At high CCh concentrations (10 microM) Ca(2+) transients in transfected and cloned cells were similar to those in control cells. In the clone exogenous IP(3)R3 lacked the C-terminal channel domain but IP(3)-binding capacity was preserved. Transfected cells mainly expressed intact type 3 IP(3)Rs but some protein degradation was also observed. We conclude that in transfected cells expression of functional type 3 IP(3)Rs causes an apparent higher affinity for IP(3). In the clone, the presence of degraded receptors leads to an efficient cellular IP(3) buffer and attenuated IP(3)-evoked Ca(2+) release.

Binding Sites↗
PubMed2002

The presence of chemokine (MCP-1, MIP-1alpha, MIP-1beta, IP-10, RANTES)-positive cells and chemokine receptor (CCR5, CXCR3)-positive cells in inflamed human gingival tissues.

Chemokines are said to be small peptides that are chemoattractants for leukocyte subpopulations within local inflammation sites. Gingival inflammation is characterized by infiltration of inflammatory mononuclear cells. The point of this study was to examine the presence or absence of chemokine-positive cells and chemokine receptor-positive cells by means of immunohistochemical methods in samples of gingival tissues obtained from patients with marginal periodontitis. Macrophage chemotactic protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, (IFN-gamma)-inducible protein-10 (IP-10) and RANTES-producing cells were found to be present in inflamed human gingival tissues. In addition, CCR5- and CXCR3-positive cells were present. In contrast, no factor expression was observed in periodontally healthy gingival tissue. Our findings suggest that these chemokines may be responsible for modulating the process of infectious disease such as marginal periodontitis.

Adult↗
PubMed1989

The dependence of sodium pump current on internal Na concentration and membrane potential in cardioballs from sheep Purkinje fibres.

The effect of various intracellular Na concentrations (CiNa) and membrane potentials on the Na pump current (Ip) was studied in isolated, cultured sheep cardiac Purkinje cells ('cardioballs'). Ip was identified as cardiac steroid sensitive current. The dependence of Ip on CiNa was investigated at a membrane potential of -40 mV by means of whole-cell recording from cardioballs internally perfused with media containing various Na concentrations. Internal perfusion with a Na free solution abolished Ip. The amplitude of Ip as a function of CiNa displayed saturation kinetics. Half maximal activation of Ip occurred at a CiNa of about 9 mM. The maximal Ip density was estimated to be 1.1 microA/cm2. The potential dependence of Ip was studied by conventional whole-cell recording under various ionic conditions. Generally Ip displayed little voltage dependence at membrane potentials positive to -20 mV. Ip declined at more negative potentials. The pump cycle probably includes only one voltage sensitive step. The potential dependence of Ip was more pronounced at lower CiNa or lower concentrations of the external pump activator Cs+. The findings are in line with the idea that increasingly steeper ionic gradients against which the cations are pumped strengthen the voltage dependence of Ip in the potential range studied. Other factors probably affecting the pump current-voltage (Ip-V) relation are discussed. The results suggest that Ip varies during electrical activity.

Animals↗
PubMed2004

Functional analysis of the green fluorescent protein-tagged inositol 1,4,5-trisphosphate receptor type 3 in Ca(2+) release and entry in DT40 B lymphocytes.

We examined the function of GFP-IP(3)R3 (green fluorescent protein-tagged inositol 1,4,5-trisphosphate receptor type 3) in Ca(2+) release and entry using a mutant DT40 cell line (IP(3)R-KO) in which all three IP(3)R genes had been disrupted. GFP-IP(3)R3 fluorescence largely overlapped with the distribution of endoplasmic reticulum, whereas a portion of GFP-IP(3)R3 apparently co-localized with the plasma membrane. The application of IP(3) to permeabilized WT (wild-type) DT40 cells induced Ca(2+) release from internal stores. Although this did not occur in IP(3)R-KO cells it was restored by expression of GFP-IP(3)R3. In intact cells, application of anti-IgM, an activator of the BCR (B-cell receptor), or trypsin, a protease-activated receptor 2 agonist, did not cause any Ca(2+) response in IP(3)R-KO cells, whereas these treatments induced oscillatory or transient Ca(2+) responses in GFP-IP(3)R3-expressing IP(3)R-KO cells, as well as in WT cells. In addition, BCR activation elicited Ca(2+) entry in WT and GFP-IP(3)R3-expressing IP(3)R-KO cells but not in IP(3)R-KO cells. This BCR-mediated Ca(2+) entry was observed in the presence of La(3+), which blocks capacitative Ca(2+) entry. Thapsigargin depleted Ca(2+) stores and led to Ca(2+) entry in IP(3)R-KO cells irrespective of GFP-IP(3)R3 expression. In contrast with BCR stimulation, thapsigargin-induced Ca(2+) entry was completely blocked by La(3+), suggesting that the BCR-mediated Ca(2+) entry pathway is distinct from the capacitative Ca(2+) entry pathway. The present study demonstrates that GFP-IP(3)R3 could compensate for native IP(3)R in both IP(3)-induced Ca(2+) release and BCR-mediated Ca(2+) entry.

Animals↗
PubMed1990

The relationship between radiosensitivity and repair of potentially lethal damage in human tumor cell lines with implications for radioresponsiveness.

The relationship between intrinsic radiosensitivity and repair capacity was studied for 22 human tumor cell lines in vitro. The experimental material was taken from 19 published papers. Parameters from three radiobiological models were used to assess this relationship: the one-hit multitarget model (D0 and n), the linear-quadratic model (alpha and beta), and the mean inactivation dose (D). Data were obtained for cells in three stages: exponentially growing cells (exp), plateau-phase cells plated immediately after irradiation (ip), and plateau-phase cells plated after completion of PLD repair (dp). No significant difference was found between radiosensitivity of exp and ip cells. There was no correlation between repair capacity and intrinsic radiosensitivity assessed with plateau-phase cells plated immediately after irradiation. The correlation studies between intrinsic radiosensitivity or repair capacity and clinical responsiveness were achieved by assigning cell lines to one of three groups of decreasing in vivo radioresponsiveness: highly, medium, and poorly responsive. There was a significant correlation between radiosensitivity and radioresponsiveness, but no correlation between repair capacity and radioresponsiveness. The average repair capacity was about 0.6 Gy, in terms of D. Three parameters, the mean inactivation dose of exponentially growing cells, of plateau-phase cells plated immediately after irradiation, and of plateau-phase cells plated after completion of PLD repair, could be used equally to assess the relationship between in vitro data and radioresponsiveness. The present results are compared to those obtained in a similar study on a group of 48 nontransformed fibroblast cell strains.

Analysis of Variance↗
PubMed1995

In situ hybridization studies of prostacyclin receptor mRNA expression in various mouse organs.

1. Expression of prostacyclin receptor (IP receptor) mRNA was examined in various mouse organs, and the cells expressing IP receptor mRNA were identified by in situ hybridization studies. Co-localization of mRNA for the IP receptor with that for preprotachykinin A (PPTA), a precursor protein for substance P, with mRNA for the prostaglandin E receptor subtypes (EP1, EP3 and EP4), and with renin mRNA, was examined by double in situ hybridization studies in the dorsal root ganglion and kidney, respectively. 2. IP receptor mRNA was expressed in the thymus and spleen. Expression in the thymus was found exclusively in the medulla, where mature thymocytes expressed transcripts for the IP receptor. Expression in the spleen was found as scattered signals over the white pulp and as punctate signals in the red pulp. The former was found in splenic lymphocytes and the latter in megakaryocytes. 3. IP receptor mRNA was also expressed in the vascular tissues of various organs such as the aorta, coronary arteries, pulmonary arteries and the cerebral arteries, where its expression was confined to smooth muscle cells. No expression was found in veins. In the kidney, IP receptor mRNA was detected in the interlobular arteries and glomerular arterioles but not in the juxtaglomerular (JG) cells which were labelled with the renin mRNA probe. 4. IP receptor mRNA was expressed in about 40% of the neurones in the dorsal root ganglion. Both small- and large-sized neurones were labelled but no labelling was found in the glia. Expression of PPTA mRNA was found in about 30% of total neurones. About 70% of these neurones expressed IP receptor mRNA, and about half of the IP receptor-positive neurones expressed PPTA mRNA. In addition to IP mRNA, mRNAs for EP1, EP3 and EP4 receptors were expressed in about 30%, 50% and 20%, respectively, of the dorsal root ganglion neurones. About 25%, 41% and 24% of the IP receptor-positive neurons co-expressed the EP1, EP3 and EP4 receptor, respectively. 5. These results not only verified IP receptor expression in various cells and tissues known to be sensitive to prostacyclin, but also revealed its expression in other systems, which urges the study of the actions of prostacyclin in these tissues. They also indicated that the actions of prostacyclin on blood vessels and platelets are mediated by the same type of receptor. Absence of IP receptor mRNA in the JG cells suggests that the action of prostacyclin on renin release may be indirect.

Animals↗
PubMed1998

IP-10 gene transcription by virus in astrocytes requires cooperation of ISRE with adjacent kappaB site but not IRF-1 or viral transcription.

Transcription of the IP-10 gene requires interferon (IFN)-stimulated response element (ISRE) and kappaB sites to be induced by lipopolysaccharide (LPS), IFN-gamma, virus, and poly(I:C). A requirement for Stat1 binding to ISRE for IFN-gamma and IFN regulatory factor-1 (IRF-1) binding to ISRE for LPS, poly(I:C), and virus has been reported. We investigated whether viral transcription is required for IP-10 induction and how ISRE interacts with IRF-1 and with two kappaB sites. IP-10 mRNA was induced by Newcastle disease virus and Sendai virus in rat astrocytes and the human astrocytoma U251 cell line. IP-10 was also induced by UV-irradiated virus, which is unable to carry out viral transcription. The minimal IP-10 virus response element (VRE) consists of an ISRE and adjacent kappaB site between -236 and -153, to which p50/p65 NF-kappaB proteins and IRF-like proteins bind. Virus induced NF-kappaB binding to an isolated kappaB sequence adjacent to ISRE. However, no protein binding to isolated ISRE was induced by virus. Virus also induced IP-10 in cells expressing a defective IRF-1 gene. Therefore, effective ISRE activity of IP-10 VRE may require an IRF-like protein binding, which is enhanced by an NF-kappaB heterodimer binding to an adjacent KB site. IRF-1 is not required for virus-induced IP-10 gene expression.

Animals↗
PubMed2000

Calcium transient activity in cultured murine neural crest cells is regulated at the IP(3) receptor.

In a previous study we have shown that cultured neural crest cells exhibit spontaneous calcium transients and that these events are required for neurogenesis. In this study, we examine the mechanism that generates these calcium transients. Extracellular Ca(2+) modulates calcium transient activity. Lanthanum (La(3+)), a general calcium channel antagonist and zero extracellular Ca(2+), reduces the percentage of cells exhibiting calcium transients (26.2 and 40. 5%, respectively) and decreases calcium spiking frequency (4.5 to 1. 0 and 2.5 to 1.0 spikes/30 min, respectively). Intracellular calcium stores also contribute to the generation of calcium transients. Depleting the calcium stores of the endoplasmic reticulum (ER) reduces the percentage of active cells (15.7%) and calcium spiking frequency (2.8 to 1.5 spikes/30 min). Ryanodine (100 microM), which blocks calcium release regulated by the ryanodine receptor (RyR), had no effect on calcium transient activity. Blocking inositol 1,4, 5-triphosphate receptor (IP(3)R)-dependent calcium release, with elevated extracellular Mg(2+) (20 mM), abolished calcium transient activity. Mg(2+) did not block caffeine-sensitive calcium release (RyR-dependent) or voltage dependent calcium channels. Mg(2+) also suppressed thimerosal-induced calcium oscillations (IP(3)R-dependent). Small increases in the intracellular calcium concentration ([Ca(2+)](i)), increases the percentage of active cells and the calcium spiking frequency, while larger increases in [Ca(2+)](i) block the transients. Reducing intracellular IP(3) levels reduces the percentage of active cells and the calcium spiking frequency. We conclude that the mechanism for generating spontaneous calcium transients in cultured neural crest cells fits the model for IP(3)R-dependent calcium excitability of the ER.

Animals↗
PubMed2005

TNF-alpha enhances phenotypic and functional maturation of human epidermal Langerhans cells and induces IL-12 p40 and IP-10/CXCL-10 production.

Dendritic cells (DC) play a central role in immunity/tolerance decision, depending on their activation/maturation state. TNF-alpha is largely produced in the skin under inflammatory conditions. However, it still remains to be defined how TNF-alpha modulates the activation status of human LC, the most specialized DC controlling skin immunity. Here, we reported that fresh immature LC, highly purified from healthy human skin and exposed for two days to TNF-alpha under serum-free conditions, expressed up-regulated level of co-stimulatory molecules (CD40, CD54, CD86), maturation markers (CD83, DC-LAMP), CCR7 lymph node homing receptor, and down-regulated Langerin level, in a dose-dependent manner. This mature phenotype is closely associated with enhanced LC allostimulatory capacity. Furthermore, TNF-alpha significantly increased the number of viable LC and decreased their spontaneous apoptosis. More importantly, TNF-alpha induced LC to produce both IFN-gamma-inducible-protein IP-10/CXCL10, a Th1-attracting chemokine and IL-12 p40. Bioactive IL-12 p70 was never detected, even after additional CD40 stimulus. The results implicate LC as an effective target through which TNF-alpha may up- or down-regulate the inflammatory skin reactions.

Antigens, CD↗
PubMed1984

The use of cytotoxic T cells in the regulation of tumour growth in syngeneic mice.

Normal C57BL/6 (B6) spleen cells were cultured with syngeneic EL4 tumour cells, expanded in IL2-containing medium, and tested for anti-tumour activity in vitro and in vivo. The activated cells were highly cytotoxic for EL4 and to a lesser degree killed syngeneic B6 blasts and allogeneic (D2) P815 tumour cells. B6 or BDF1 mice that received these cultured cells by IP injection cleared 125IUdR-labelled EL4 cells faster than untreated mice. However, this enhanced clearance was evident only 7-12 days after injection. Since the injected cells had a short half-life (less than 10% remaining after 48 h) the effect of these cells in vivo was most probably due to the activation of the host's immune system. Mice that received cultured cells survived significantly longer than untreated mice following a lethal dose of EL4 cells. Cultured cells were much more effective in prolonging survival when used in conjunction with cyclophosphamide (CY). In animals receiving either cultured cells with or without CY or CY alone tumour clearance was markedly enhanced 7-12 days after injection. When challenged with a small dose of EL4 tumour cells (1 X 10(4) SC per mouse) three of ten B6 mice treated with B6 anti-EL4 cultured cells were able to survive indefinitely. The frequency of CTL precursors to EL4 from the spleen cells of these surviving animals was about five-fold higher than that of normal spleen cells. Furthermore, CTL derived from primed spleen cells were more specific for EL4 than those derived from normal spleen cells.

Animals↗
PubMed1987

BK virus in cell culture: infectivity quantitation and sequential expression of antigens detected by immunoperoxidase staining.

We applied an indirect immunoperoxidase staining method for the detection of BK virus (BKV) antigens in Vero cells. By immunoperoxidase staining of sequential samples, expression of BKV T- and structural antigens was first detectable 72 h postinfection (pi). The initial low number of antigen positive cells was slowly increasing until 6 d pi. Thereafter, a steady progression was observed until total cytopathogenic effect 30 d pi. Viral hemagglutinins were detected 11 d pi in both the culture medium and in the cell lysate. Passage of the preparations into fresh Vero cells and immunoperoxidase detection demonstrated the presence of infectious virions in both the cell lysates and the medium from 2 d pi. The number of infectious particles in both media and cell lysates correlated to the number of IP stained cells in the sequential staining. We suggest that this type of assay might be used to examine the effects, in vitro, of interferons and other virostatic drugs of BKV and other viruses.

Animals↗
PubMed1997

Histologic correlates of angiographic chronic total coronary artery occlusions: influence of occlusion duration on neovascular channel patterns and intimal plaque composition.

OBJECTIVES: Age-related changes in histologic composition and neovascular channel (NC) pattern of angiographic chronic total coronary artery occlusions (CTOs) were studied to define histologic correlates of age-related revascularization profiles and neovascular channel formation. BACKGROUND: Revascularization of CTOs is frequently characterized by inability to cross or dilate the lesion and a high incidence of reocclusion or restenosis but low periprocedural ischemic complication rates. Little is known about the histopathologic basis of these observations. METHODS: Ninety-six angiographic CTOs from autopsy studies in 61 patients who had undergone coronary angiography within 3 months of death were studied. Abrupt plaque rupture was excluded. Occlusion segments were analyzed for 1) histologic composition as a function of lesion age; and 2) NC pattern as a function of lesion age and intimal plaque (IP) composition. RESULTS: Cholesterol and foam cell-laden IP was more frequent in younger lesions (p = 0.0007), whereas fibrocalcific IP increased with CTO age (p = 0.008). IP NCs arose directly from adventitial vasa vasorum and were anatomically and quantitatively related in terms of number and size (p = 0.0001) to the extent of IP cellular inflammation. IP cellular inflammation exceeded that found in the adventitia (p < 0.001) or media (p = 0.0001) across all CTO ages. In CTOs < 1 year old, the adventitia was associated with a larger number and size of NCs relative to the IP (p = 0.0006 and p = 0.009), media (p = 0.0001 and p = 0.002) and recanalized lumen (p = 0.0001 and p = 0.001). In CTOs >1 year old, the adventitia and IP NC numbers were similar and exceeded NC numbers found in the media (p = 0.0001) and recanalized lumen (p = 0.0001 and p = 0.003). CONCLUSIONS: Angiographic CTO frequently corresponds to less than complete occlusion by histologic criteria. Age-related changes in IP composition from cholesterol laden to fibrocalcific may explain the adverse revascularization profile of older CTOs. IP NC growth derived from the adventitia increases with age and is strongly associated with IP cellular inflammation. IP NC formation may protect against the flow-limiting effects of IP growth.

Adult↗
PubMed2005

IP-10 mediates selective mononuclear cell accumulation and activation in response to intrapulmonary transgenic expression and during adenovirus-induced pulmonary inflammation.

CXC chemokines that lack the glutamine-leucine-arginine (ELR) motif, including interferon (IFN)-inducible protein 10 (IP-10 or CXCL10), have been shown to mediate the generation of type 1 immune responses. In this study, we found that the intrapulmonary transient transgenic expression of murine IP-10 in mice using adenoviral gene transfer resulted in the early accumulation of neutrophils, natural killer (NK) cells, and NK T cells within the lung, followed by the delayed accumulation of CD4+ T cells. Adenovirus-mediated transgenic expression of IP-10 also resulted in selective activation of mononuclear cells, including gamma(delta)-T cells and NK cells, as manifest by CD69 expression or induction of cell-associated IFN-gamma. Importantly, the intratracheal (i.t.) administration of a control human type 5 adenovirus also caused significant accumulation of NK, NK T, and CD4+ T cells, which was maximal at 7 days post vector administration and was associated with the induction of IP-10. Neutralization of endogenous IP-10 in animals receiving control adenovirus resulted in decreases in the numbers of NK, CD4+, and CD8+ T cells. These results indicate that IP-10 can direct the accumulation and activation of neutrophils and selected mononuclear cells to the lung and that adenovirus-induced IP-10 contributes to lung inflammatory cell recruitment/activation observed in response to adenoviral vectors used for gene therapy.

Adenoviridae↗
PubMed2003

An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as functional receptor for platelet factor 4.

The chemokines CXCL9/Mig, CXCL10/IP-10, and CXCL11/I-TAC regulate lymphocyte chemotaxis, mediate vascular pericyte proliferation, and act as angiostatic agents, thus inhibiting tumor growth. These multiple activities are apparently mediated by a unique G protein-coupled receptor, termed CXCR3. The chemokine CXCL4/PF4 shares several activities with CXCL9, CXCL10, and CXCL11, including a powerful angiostatic effect, but its specific receptor is still unknown. Here, we describe a distinct, previously unrecognized receptor named CXCR3-B, derived from an alternative splicing of the CXCR3 gene that mediates the angiostatic activity of CXCR3 ligands and also acts as functional receptor for CXCL4. Human microvascular endothelial cell line-1 (HMEC-1), transfected with either the known CXCR3 (renamed CXCR3-A) or CXCR3-B, bound CXCL9, CXCL10, and CXCL11, whereas CXCL4 showed high affinity only for CXCR3-B. Overexpression of CXCR3-A induced an increase of survival, whereas overexpression of CXCR3-B dramatically reduced DNA synthesis and up-regulated apoptotic HMEC-1 death through activation of distinct signal transduction pathways. Remarkably, primary cultures of human microvascular endothelial cells, whose growth is inhibited by CXCL9, CXCL10, CXCL11, and CXCL4, expressed CXCR3-B, but not CXCR3-A. Finally, monoclonal antibodies raised to selectively recognize CXCR3-B reacted with endothelial cells from neoplastic tissues, providing evidence that CXCR3-B is also expressed in vivo and may account for the angiostatic effects of CXC chemokines.

Alternative Splicing↗
PubMed2006

Differential regulation of hyaluronan-induced IL-8 and IP-10 in airway epithelial cells.

Airway epithelium is emerging as a regulator of local inflammation and immune responses. However, the cellular and molecular mechanisms responsible for the immune modulation by these cells have yet to be fully elucidated. At the cellular level, the hallmarks of airway inflammation are mucus gland hypertrophy with excess mucus production, accumulation of inflammatory mediators, inflammation in the airway walls and lumen, and breakdown and turnover of the extracellular matrix. We demonstrate that fragments of the extracellular matrix component hyaluronan induce inflammatory chemokine production in primary airway epithelial cells grown at an air-liquid interface. Furthermore, hyaluronan fragments use two distinct molecular pathways to induce IL-8 and IFN-gamma-inducible protein 10 (IP-10) chemokine expression in airway epithelial cells. Hyaluronan-induced IL-8 requires the MAP kinase pathway, whereas hyaluronan-induced IP-10 utilizes the NF-kappaB pathway. The induction is specific to low-molecular-weight hyaluronan fragments as other glycosaminoglycans do not induce IL-8 and IP-10 in airway epithelial cells. We hypothesize that not only is the extracellular matrix a target of destruction in airway inflammation but it plays a critical role in perpetuating inflammation through the induction of cytokines, chemokines, and modulatory enzymes in epithelial cells. Furthermore, hyaluronan, by inducing IL-8 and IP-10 by distinct pathways, provides a unique target for differential regulation of key inflammatory chemokines.

Binding Sites↗
PubMed2002

Expression of CXC chemokine IP-10 in testicular germ cell tumours.

Tumour-infiltrating T lymphocytes (TILs) possess discrepant properties ranging from anti- to protumour activities. Understanding precisely which mechanisms navigating T lymphocytes into the tumour site will help to further the anti-tumour or to disrupt the pro-tumour activities of TILs. The present study asked what enables TILs to migrate into testicular germ cell tumours (TGCTs). TILs were characterized and the expression of a large panel of T-lymphocyte-attracting chemokines was investigated in 21 TGCT cases. Flow cytometry revealed that approximately 80% of TGCT-infiltrating T lymphocytes express CXCR3, a receptor for the chemokine interferon-inducible protein-10 (IP-10). RT-PCR and immunohistochemistry indicated that IP-10 was the only chemokine investigated which was constantly expressed in TGCT. As IP-10 was found to be expressed by endothelial cells of TGCT-associated blood vessels, the question arose whether the IP-10-regulating cytokine interferon-gamma (IFNgamma) is produced by tumour cells and if so, whether tumour-derived IFNgamma can induce IP-10 in endothelial cells. Applying in situ hybridization, IFNgamma transcripts were found in neoplastic germ cells. Analyses of two TGCT cell lines indicated that the tumour cells not only express IFNgamma mRNA, but also produce and secrete IFNgamma protein; tumour-derived IFNgamma provokes IP-10 expression and secretion by endothelial cells in vitro, as assessed by PCR and ELISA. Together, the data suggest that neoplastic germ cells secret IFNgamma and thereby stimulate tumour-associated endothelial cells to express IP-10, which contributes to the recruitment of CXCR3+ T lymphocytes to the site of TGCTs.

Adult↗
PubMed1985

Treatment of primary radiogenic C57BL mouse cell leukemia/lymphoma by 1,3-bis(2-chloroethyl)-1-nitrosourea chemotherapy and adjuvant cellular therapy.

Primary radiation-induced or radiation leukemia virus (RadLV)-induced T-leukemias/lymphomas were treated in vivo in an early to advanced state by using 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). BCNU was given at various times after the tumor induction procedure. Death from RadLV lymphomas which had been initiated in 33 +/- 3 day old C57BL mice by intrathymic injection of RadLV was scored in untreated, BCNU-treated or BCNU and cellular adjuvant treated mice. Intrathymic RadLV injection in 33 +/- 3 day old mice produced tumors in 98% of injected mice. Median survival time (MST) was increased by BCNU and by BCNU plus bone marrow cell therapy whether done 33 or 47 days after RadLV. There was increased in MST from 108 days to 171 days by BCNU and bone marrow cell therapy given 33 days after tumor initiation and to 195 days when therapy was given 47 days after initiation. In radiation-induced lymphomas produced by 190 rad every week X 4 of 33 +/- 3 day old mice, spleen cell (X 1) therapy or BCNU treatment increased the MST of treated mice from 142 days to 177 days after iv spleen cells or to 195 days after iv-ip spleen cells, and this protocol produced 31% long-term cures. Cellular adjuvant therapy combined with BCNU chemotherapy was effective for curing the lymphomas but cellular adjuvant therapy alone was also highly effective for therapy.

Animals↗