Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “MIF”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 181 records · Page 10Linked to original sources
PubMed1998

Identification of macrophage migration inhibitory factor (MIF) in human vascular endothelial cells and its induction by lipopolysaccharide.

Cytokines play an important role in inflammation and immunity. In this study, the authors examined expression of macrophage migration inhibitory factor (MIF) in vascular endothelial cells, using human umbilical vein endothelial cells (HUVEC), by reverse transcription-polymerase chain reaction (RT-PCR)/Southern blot, Western blot analysis, and immunohistochemistry. The RT-PCR/Southern blot showed that MIF mRNA was exceedingly upregulated by the stimulation of lipopolysaccharide (LPS) and reached the maximum 12 h after the stimulation. At the range of 10 pg/ml to 10 ng/ml of LPS, the MIF mRNA expression was induced in a dose-dependent manner, but drastically decreased at doses of more than 100 ng/ml. Western blot analysis and immunohistochemistry using an anti-human MIF antibody revealed the presence of MIF protein in cytoplasm of the unstimulated cells. The precise pathophysiological role of MIF in HUVEC has not been fully understood; however, the upregulation of MIF mRNA expression in vascular endothelial cells by LPS stimulation suggests the possibility that the cytokine plays an important role in systemic inflammatory events such as endotoxaemia.

Animals↗
PubMed1987

Long-term hyperalgesia induced by neonatal beta-endorphin and morphiceptin is blocked by neonatal Tyr-MIF-1.

Male rats were injected s.c. once daily during the first week of life with beta-endorphin (BE), morphiceptin, the antiopiate Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), or one of the two opiate peptides in combination Tyr-MIF-1. Pups treated with neonatal BE removed their tails from a series of increasingly hot water baths significantly faster than controls on day 9, confirming our earlier studies. In addition, we found that Tyr-MIF-1 blocked this effect of BE. At 4.5 months, latency to lick a hindpaw in the hot-plate test was significantly faster in groups given BE alone, morphiceptin alone, or the control vehicle than in any of the 3 groups given Tyr-MIF-1. At 6 months the two groups given opiate peptides alone showed faster tail-flick latencies than the controls and the groups given Tyr-MIF-1. These results indicated that the long-term nociceptive changes induced by the opiate peptides were opposite to those induced by Tyr-MIF-1. Mean tail-flick latencies of the groups on day 9 correlated well with hot-plate and tail-flick scores in adulthood, indicating that the effects of the peptides were persistent. The neonatal peptide treatments did not differentially affect the analgesia induced by the stress of footshock or warm-water swim. Rats given either of the opiate peptides alone tended to fall off a rotorod faster than those in the other groups. These results support the role of Tyr-MIF-1 as an antiopiate and further illustrate the long-term effects of neonatally administered peptides.

Animals↗
PubMed1996

Identification of macrophage migration inhibitory factor (MIF) in human skin and its immmunohistochemical localization.

The presence and tissue localization of macrophage migration inhibitory factor (MIF) in human skin were examined. Reverse transcription-polymerase chain reaction analysis revealed that MIF mRNA was expressed in both surgically obtained normal human epidermis and primary cultured human keratinocytes. The expression of MIF was further confirmed by Western blot analysis, which demonstrated a single band at about 12.5 kDa using a polyclonal antibody against human recombinant MIF. Immunohistochemical studies showed that MIF existed in human epidermis, especially in the basal layer. The pathophysiological role of MIF in human skin remains undefined; however, the present results indicate that MIF may play an important role in immunity, inflammation and cellular differentiation of epidermal cells.

Animals↗
PubMed1980

Radioimmunoassay of MIF-1/Tyr-MIF-1-like material in rat pineal.

The hypothalamic peptide MIF-1 (Pro-Leu-Gly-NH2) was coupled to thyroglobulin and injected into rabbits. The resulting antiserum reacted with the tetrapeptide Tyr-MIF-1 to a greater extent than with the tripeptide MIF-1, presumably because of a better conformation for antibody binding. By radioimmunoassay (RIA), immunoreactive MIF-1/Tyr-MIF-1-like material was found in the pineal gland of each of the 100 rats examined. The tendencies for slightly higher levels in pineals obtained from rats kept in constant darkness for two weeks, from rats in a normal light cycle decapitated at noon, or from rats which had been hypophysectomized were not statistically significant. Gel filtration of pineal extracts on a column of Sephadex G-10 revealed that by RIA one immunoreactive peak eluted near MIF-1 and oxytocin, and another peak near Tyr-MIF-1. The results suggest the presence in pineal tissue of an MIF-1-like material as well as a novel peptide containing Tyr-Pro-Leu-Gly-NH2 or a closely related structure for which oxytocin is unlikely to be the precursor.

Animals↗
PubMed1994

Central administration of Tyr-MIF-1 stimulates gastrointestinal motility in rats: evidence for the involvement of dopamine, sigma and CCK receptors.

The effect of central administration of the endogenous peptide Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) on the gastrointestinal myoelectric activity and its mechanism of action were studied in rats. Tyr-MIF-1 (40 & 80 micrograms/kg i.c.v.) stimulated antral and duodenal myoelectric activity in a multiphasic manner. On the antrum it induced a primary increase of the frequency of antral spike bursts followed by a consecutive return to control value and a second rise of the frequency. Likewise duodenal migrating myoelectric complexes (MMCs) were initially disrupted and replaced by an irregular spiking activity followed by a reaparition of the phase III of the MMCs with increased amplitude and frequency. Haloperidol (1 mg/kg i.p.) blocked all the effects of Tyr-MIF-1 whereas sulpiride (5 mg/kg s.c.) blocked only the duodenal stimulation without affecting that on the antrum. Similarly BMY-14802 (0.5 mg/kg s.c.) antagonized selectively the primary antral stimulation and the initial disruption of duodenal MMC induced by Tyr-MIF-1. L365 260 (10 micrograms/kg i.c.v.) has also antagonized only the initial disruption of duodenal MMCs. DTG and JO 1784 (100 micrograms/kg i.c.v. each) reproduced fully the effect of Tyr-MIF-1 on the duodenum but not that on the antrum. Domperidone, (+)SCH 23390, devazepide, PK 11-195 and flumazenil did not have effect on the action of Tyr-MIF-1. It is concluded that Tyr-MIF-1 stimulates the antrum involving haloperidol sensitive but nondopamine, dopamine, probably sigma receptors, and the duodenum via a pathway where central D2 dopamine, sigma and CCKB receptors are implied.

Action Potentials↗
PubMedDate not supplied

MIF-1 attenuates spiroperidol alteration of striatal dopamine D2 receptor ontogeny.

Long-term postnatal treatment of rats with the dopamine D2 receptor antagonist, spiroperidol, results in the impaired development of striatal D2 receptors. Because the tripeptide prolyl-leucyl-glycinamide (MIF-1) attenuates haloperidol-induced up-regulation of striatal dopamine D2 receptors in adult rats, we studied the effect of MIF-1 on the spiroperidol-induced alteration of striatal D2 ontogeny. Postnatal treatment of rats with spiroperidol (1.0 mg/kg/day, IP, x32 days from birth) resulted in a 74% decrease in the Bmax for [3H]spiroperidol binding with no change in the Kd at 5 weeks. When rats were studied at 8 weeks, in the absence of additional treatment, total specific [3H]spiroperidol binding was reduced by 59%. While MIF-1 alone (1.0 mg/kg/day, IP, x32 days from birth) had no effect on [3H]spiroperidol binding, MIF-1 completely attenuated the ontogenic impairment of striatal D2 receptors that was produced by spiroperidol treatment. At 5 weeks the Bmax for [3H]spiroperidol binding was at the saline control level in the group of rats cotreated with spiroperidol and MIF-1. At 8 weeks, with no additional treatments, the specific binding of [3H]spiroperidol to striatum was also at control levels in the group cotreated with spiroperidol and MIF-1. These findings demonstrate that MIF-1 attenuates spiroperidol-induced impairment of development of striatal dopamine D2 receptors in rats.

Animals↗
PubMedDate not supplied

MIF-1 fails to modify agonist-induced oral activity in neonatal 6-OHDA-treated rats.

L-Prolyl-L-leucyl-glycinamide (MIF-1) is known to attenuate apomorphine-induced stereotypes in adult rats that are lesioned as neonates with 6-hydroxydopamine (6-OHDA). To test whether MIF-1 would affect dopamine (DA) agonist-induced and serotonin (5-HT) agonist-induced oral activity, both intact and neonatal 6-OHDA-treated rats were studied. Rats at 3 days from birth were injected with desipramine (20 mg/kg, IP), 1 h before 6-OHDA HBr (100 micrograms, salt form, in each lateral ventricle) or its vehicle, saline-ascorbic acid (0.1%). At approximately 6 months rats were treated with MIF-1 (0.1, 1.0, or 10.0 mg/kg, IP), 10 min before SKF 38393 HCl (1.0 mg/kg, IP) or m-chlorophenylpiperazine 2HCl (m-CPP 2HCl; 0.5 mg/kg, IP), DA D1 and 5-HT1C,2 receptor agonists, respectively. Although both agonists increased oral activity in control and neonatal 6-OHDA-treated rats, MIF-1 did not modify the response. In rats that received either of the three doses of MIF-1 for 21 consecutive days, there was still no observed effect of MIF-1 on the oral response of control and 6-OHDA-lesioned rats to SKF 38393 and m-CPP. These findings indicate that MIF-1 does not modify the oral activity response of supersensitized D1 and 5-HT1C receptors in adult rats that are lesioned neonatally with 6-OHDA.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1996

Presence of macrophage migration inhibitory factor (MIF) in ependyma, astrocytes and neurons in the bovine brain.

We investigated the immunohistochemical localization of a cytokine macrophage migration inhibitory factor (MIF) in the bovine brain. MIF was present in the ependymal cell linings of the cerebral ventricles throughout. Double immunostaining of the section with anti-glial fibrillary acidic protein (GFAP) antibody and with anti-MIF antibody showed that the astrocytes present in subependymal layer were immunoreactive for MIF. In the hippocampus, the pyramidal cells in the CA3 and CA4 subfields and the granule cells of the dentate gyrus were immunoreactive. The bundles of mossy fibers were stained along their projections to CA3 and CA4 regions. The nuclei of the subpopulation of these MIF-immunoreactive cells were also immunostained. These results indicated the widespread distribution of a cytokine, MIF, in the bovine brain and suggested the possibility that MIF might play additional roles than a proinflammatory mediator role in the brain.

Animals↗
PubMedDate not supplied

Striatal dopamine turnover and MIF-I.

Because of conflicting reports of the actions of the antiparkinsonian agent L-prolyl-L-leucyl-glycine amide (PLG, MIF-I) on the turnover of striatal dopamine (DA), this process was reinvestigated. In the present series of studies, it was found that neither our MIF-I (200 ng ICV) nor the MIF-I used by Versteeg et al. [25] was effective in altering the rate of decline of endogenous DA in the caudate nucleus of rats pretreated with alpha-methyl-p-tyrosine (300 mg/kg IP). In addition, our MIF-I (1 mg/kg IP) did not change endogenous dihydroxyphenylacetic acid (DOPAC) or homovanillic acid (HVA) in rat striatum. These studies indicate that MIF-I does not alter the turnover rate of DA in nigrostriatal neurons. It is possible that MIF-I or some substance released by MIF-I acts at a postsynaptic receptor site.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

In vitro studies of Tyr-MIF-1 with human lymphocytes.

Our previous report showed that the brain peptide Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) blocks the inhibitory effect of morphine sulfate on E-rosette formation by human peripheral blood lymphocytes (PBL). In this study, additional in vitro effects of Tyr-MIF-1 on human PBL were studied. The percentages of positive cells for CD 2, a sheep erythrocyte receptor, CD 4 and CD 8 were unchanged after incubation of PBL with morphine or morphine plus Tyr-MIF-1. Tyr-MIF-1 was not mitogenic by itself. The addition of Tyr-MIF-1 did not increase the proliferative response of PBL to Con A, although morphine did. Tyr-MIF-1 did not activate PBL to produce IL 2 nor did it affect the production of IL 2 by Con A-stimulated PBL. The results suggest that Tyr-MIF-1 does not directly modulate CD 2, CD 4 and CD 8 expression, does not alter the proliferative response of PBL, and does not affect the production of IL 2.

Antigens, CD↗
PubMed2026

MIF-CD74 axis facilitates MDSC infiltration in the tumor microenvironment of pancreatic ductal adenocarcinoma.

Immune checkpoint inhibitors show insufficient efficacy against pancreatic ductal adenocarcinoma (PDAC). The tumor microenvironment (TME) has a remarkable influence on responsiveness to cancer immunotherapy. The aim of this study was to investigate immunosuppressive characteristics of TME in PDAC tissues. The flow cytometry (FCM) of PDAC surgical specimens revealed that the profile of tumor-infiltrating leukocytes was classified into myeloid cell- and T-cell-dominant subtypes; the myeloid subtype was associated with poorer patient outcomes. Myeloid-derived suppressor cells (MDSCs) showed the highest hazard ratio among various myeloid cell types. Single-cell RNA sequencing and FCM revealed that most MDSCs, but not lymphocytes, in PDAC tissues characteristically express CD74. Macrophage migration inhibitory factor (MIF), a CD74 ligand, was highly expressed in cancer-associated fibroblasts (CAFs) and cancer cells. Spatial transcriptomics demonstrated that the MIF-CD74+ myeloid cell interaction was recognized in CAF-dominant areas in PDAC tissue. CAFs expressing immune suppressor molecules such as MFAP5 and LRRC15 were consistent with MIF+ CAFs. Furthermore, MIF+ CAFs enhanced the migratory activity of MDSCs and promoted MDSC induction and activation. In the murine model, MDSCs were significantly increased in MIF-expressing PDAC tumors, as were CD74+ M-MDSCs per M-MDSC, confirming in vivo interaction between CD74 and MIF. MDSCs play a crucial role in creating an immunosuppressive TME in PDAC; the MIF-CD74 axis drives interactions between MDSCs and CAFs.

Humans↗
PubMed2006

Tumor-derived macrophage migration inhibitory factor (MIF) inhibits T lymphocyte activation.

Macrophage migration inhibitory factor (MIF) is a multi-functional cytokine that is considered a pro-inflammatory cytokine. However, our studies show that MIF, when produced in super-physiological levels by a murine neuroblastoma cell line (Neuro-2a) exceeding those normally seen during an immune response, inhibits cytokine-, CD3-, and allo-induced T-cell activation. MIF is also able to inhibit T cells that have already received an activation signal. The T-cell inhibitory effects of culture supernatants from neuroblastoma cells were reversed when the cells were transfected with dicer-generated si-RNA to MIF. When T cells were activated in vitro by co-culture with interleukin (IL)-2 and IL-15 and analyzed for cytokine production in the presence or absence of MIF-containing culture supernatant, inhibition of T-cell proliferation and induced cell death were observed even as the treated T cells produced high levels of interferon-gamma (IFN-gamma). The inhibitory effects of MIF were partially reversed when lymphocytes from IFN-gamma knockout mice were tested. We propose that the high levels of MIF produced by neuroblastoma cause activation induced T-cell death through an IFN-gamma pathway and may eliminate activated T cells from the tumor microenvironment and thus contribute to escape from immune surveillance.

Animals↗
PubMed2005

Gender-related effects of chronic non-malignant pain and opioid therapy on plasma levels of macrophage migration inhibitory factor (MIF).

Macrophage migration inhibitory factor (MIF) is a cytokine produced by neuroendocrine and immune tissues that possesses several characteristics of a neuroendocrine mediator. Chronic pain is known to affect and to be affected by neuroendocrine and immune mechanisms. In the present study, the plasma levels of MIF and several hormones (cortisol, estradiol, testosterone) were determined to evaluate their mutual behaviour in controls and in chronic pain patients. Blood samples were collected from males and females divided into groups depending on their age (younger or older than 55) and health condition: (1) pain-free control subjects; (2) chronic non-malignant pain subjects. Moreover, two additional groups were added to evaluate the effects of short- and long-term opioid administration: (3) short-term opioid-treated chronic pain patients and (4) long-term opioid-treated chronic pain patients (longer than 6 months). MIF in control/younger men was higher than in all the other control and chronic pain groups. MIF was lower in pain patients than in controls of both sexes. MIF was not changed by morphine administration; its levels remained lower in opioid-treated subjects than in controls after both short- and long-lasting administration. Chronic pain changed hormone plasma levels differently in male and female patients. MIF was positively correlated with testosterone and negatively with estradiol. These results demonstrate sex differences in the younger men and women and a strong pain-induced decrease of MIF availability. These findings suggest the involvement of this cytokine in the sex differences observed in chronic pain conditions.

Adult↗
PubMed2002

The mif gene is transcriptionally regulated by glucose in insulin-secreting cells.

Macrophage migration inhibitory factor (MIF) is an important regulator of glucose homeostasis. In pancreatic beta-cells, MIF expression is regulated by glucose and its secretion potentiates the glucose-induced insulin secretion. The molecular mechanisms by which glucose mediates its effect on MIF expression are not elucidated. Herein, we report that incubating the differentiated insulin-secreting cell line INS-1 in high glucose concentration increases MIF transcriptional activity as well as the reporter gene activity driven by the -1033 to +63 bp fragment of the MIF promoter. A minimal region located between -187 and -98 bp of this promoter sequence contributes both to basal activity and glucose-responsiveness of the gene. Within this promoter region, two cis-binding sequences were identified by mobility shift assays and footprinting experiments. Both cis-elements interact with nuclear proteins expressed specifically in insulin-secreting cells. In conclusion, we identified a minimal region of the MIF promoter which contributes to the glucose stimulation of the mif gene in insulin-secreting cells.

Animals↗
PubMed2000

Expression and glucocorticoid regulation of macrophage migration inhibitory factor (MIF) in hippocampal and neocortical rat brain cells in culture.

The biosynthesis of macrophage-migration inhibitory factor (MIF) and its regulation by the glucocorticoid dexamethasone was examined in cultured hippocampal and neocortical embryonic rat cells. Using immunohistochemical methods, MIF was found to be localized in neuronal as well as in non-neuronal cells. During the whole 12 day culture period, levels of MIF transcripts were detectable in both hippocampal and neocortical cells with an apparent increase in extracellular MIF protein at the later time points examined. Treatment with even very low concentrations (10(-11) M) of dexamethasone did not alter MIF mRNA levels but resulted in a rapid release of intracellular MIF protein within 1 and 4 h and a subsequent replenishment after 24 h. These data suggest that glucocorticoids do not affect the transcriptional activity of the MIF gene but induce the secretion of the protein, which suggests a close functional relationship of both mediators in the CNS.

Animals↗
PubMed1984

Some analogs of Tyr-MIF-1 affect passive avoidance behavior but not motor activity in rats.

The effects of three analogs of the brain peptide Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) were tested in several behavioral tests after peripheral injection in rats. In the passive avoidance test, rats injected SC with 1 mg/kg Ala-MIF-1 or Phe-MIF-1 entered the second compartment of two-chamber shuttle box significantly faster than did rats receiving diluent. Leu-MIF-1 failed to produce significantly faster entry compared to diluent. None of the peptides significantly affected ambulation, rearing, or defecation. Flinch and escape thresholds were not affected by Ala-MIF-1, the only analog tested for this behavior. The results demonstrate that some analogs of Tyr-MIF-1 can exert behavioral effects similar to those exerted by the parent compound whereas other analogs resemble MIF-1 in being inactive under these experimental conditions.

Animals↗
PubMed2000

Different influence of macrophage migration inhibitory factor (MIF) in signal transduction pathway of various T cell subsets.

It has been shown that macrophage migration inhibitory factor (MIF) modulates not only macrophage functions, but also T cell functions. However, detailed analysis of the MIF function on responses of various T cell subpopulations remained to be elucidated. In this report, using a neutralizing anti-MIF monoclonal antibody (mAb) we examined MIF functions on various T cell lineages. It was shown that anti-MIF mAb inhibited antigen-specific responses of both IFN-gamma producing and IL-4 producing T cells. The inhibition appeared to be related to blockade of the signal pathway via T cell receptor (TCR) but not that via IL-2 receptor (IL-2R). However, the anti-MIF mAb showed no inhibitory effect on NK-T cell responses stimulated through TCR. These results suggest that MIF is involved in the signal pathway via TCR in mainstream T cells but not in NK-T cells.

Amino Acid Sequence↗
PubMed1986

Suppression of migration inhibition factor (MIF) production by mitomycins in vitro.

The effects of a series of mitomycins in a modified version of the Migration Inhibition Factor (MIF) test were investigated. This modified assay, which uses monocytes of the mouse cell line WEHI3 as target cells for MIF, discriminates between effects on the migrating monocytes, the production of MIF by lymphocytes and the activity of the produced MIF. The 7-methoxy mitomycins were found to be more active than the 7-amino and 7-hydroxy derivatives in suppressing both the spontaneous migration of target monocytes and the MIF production by lymphocytes. Neither of the compounds had a significant effect on the activity of produced MIF. A relationship between the activities of the mitomycins and their lipophilicity and polarographic half-wave potential is discussed. Further attention is paid to the stability of the mitomycins under the test conditions and additional advantages of the modified MIF assay over related in vitro tests for cell-mediated immunity.

Animals↗