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J Uksila

Publications and source records attributed to J Uksila.

35 records · Page 2Linked to original sources

Trans-urocanic acid, a natural epidermal constituent, inhibits human natural killer cell activity in vitro.

UV irradiation has been reported to influence NK cell function both in vitro and in vivo. Since urocanic acid may mediate UV-induced immune modulation we tested the effect of trans- and cis-urocanic acid (UCA) on the cytotoxic activity of human peripheral blood lymphocytes against the erythroleukemic target cell line K562 in vitro. Trans-UCA was found to be a strong inhibitor of NK cell activity whereas cis-UCA had no effect. Trans-UCA also partially inhibited cytotoxic function of IL-2-activated NK cells and reduced IL-2-induced activation of NK cells. This is the first report describing trans-UCA to be active, and cis-UCA inactive, in regulating an immune function. In the skin, a decrease in epidermal trans-urocanic acid concentration by UV radiation could produce a favorable milieu for NK cell activity, and thus counteract the impairment of antigen-specific immune surveillance, induced by increased cis-urocanic acid concentrations.

Cells, Cultured↗

Effects of cis- and trans-urocanic acids on the secretion of interleukin-1 beta and tumour necrosis factor-alpha by human peripheral blood monocytes.

In order to investigate the mechanism of urocanic acid (UCA)-mediated immune modulation, we studied the effect of cis- and trans-UCA on interleukin-1 beta and tumour necrosis factor-alpha production by human peripheral blood monocytes, using immunospecific ELISA techniques. Trans-UCA augmented the interleukin-1 beta production and inhibited tumour necrosis factor-alpha production in a dose-dependent manner, whereas cis-UCA had no effect on the secretion of these cytokines by phorbol myristate acetate or lipopolysaccharide-stimulated monocytes. This is a novel example of trans-UCA mediating a biological effect, a finding earlier reported for cyclic adenosine monophosphate up-regulation in human fibroblasts by Palaszynski and coworkers and for human natural killer cell inhibition by ourselves. Our data suggest an important role for trans-UCA as an immunomodulator in the skin.

Dose-Response Relationship, Drug↗

Testis physiology relevant to immunoregulation.

Intra-testicular transplants are placed in rodents into the large lymphatic sinusoids of the interstitial tissue of the testis. These sinusoids are filled with a protein-rich extracellular fluid that supplies all the requirements of the grafts until vascularization takes place. The testicular microvascular endothelium regulates transport of T lymphocytes and immunoglobulin G to the testis and may thus contribute to regulation of the immune system in this organ. Differences in the organization of the lymphatic drainage exist between species, but in every studied species lymphatic drainage from the testis leads to lymph nodes.

Animals↗

Activation of the immune system in the testis.

The present concept for the mechanism of prolonged transplant survival in the testis suggests that lymphocyte activation is inhibited locally in this site by testicular products. As the testis produces several immunoregulatory factors, the behaviour of lymphocytes in the testis may depend on the net effect of all these factors on intralymphocytic events. In the present article, the extra- and intracellular events associated with lymphocyte activation are reviewed and the steps of lymphocyte activation which might be subject to interference by testicular factors are identified.

Animals↗

Testicular immunosuppressive protein.

Auto-, allo- and xenografts of various endocrine tissues survive for prolonged periods in the testicular interstitium. The reason for transplant survival outside the blood-testis barrier has been obscure. In the present paper we describe a high molecular weight (Mr = 130,000), heat- and pH-labile immunosuppressive factor with an isoelectric point of 6.3-7.3 in extracellular fluid collected from the rat testicular interstitium. The results show that the testicular immunosuppressive agent is not a steroid, but a protein. This testicular immunosuppressive protein may contribute to the immune privilege in the testicular interstitium.

Animals↗

Sensitivity of human fetal hemopoietic cells to NK cell-mediated lysis.

Hemopoietic cells from human fetal livers at 11 to 18 weeks of gestational age were studied as to whether they were sensitive to adult and autologous fetal NK cells. Cell line K562 was used as control target in the 51Cr release assay and in the cold target competition assay. Adult peripheral blood NK cells did not kill liver-derived hemopoietic cells of four fetuses tested. Neither did fetal liver cells, whether or not expressing spontaneous cytotoxicity against K562 cells, destroy autologous hemopoietic liver cells. Hemopoietic liver cells from six fetuses were studied in the cold target competition assay. Liver cells of two fetuses clearly competed with lysis of K562 cells by adult NK cells. Thymus cells from one 18 week-old fetus had a weak capacity to compete with lysis of K562 cells by adult cells, whereas cells from the spleen and liver of the same fetus did not. It is concluded that early fetal liver hemopoietic cells are not susceptible to lysis by NK cells but an interaction between fetal cells and NK effector cells results in a depressed NK cell activity against NK-sensitive target cells.

Cytotoxicity, Immunologic↗

Human NK cell activity is not inhibited by pregnancy and cord serum factors and female steroid hormones in vitro.

The effects of female sex steroid hormones and of pregnancy and cord sera on human NK cell activity against the NK sensitive K562 cells were studied. The cytotoxicity of adult peripheral blood lymphocytes was measured after incubation of peripheral blood effector cells in vitro with estrone, 17 beta-estradiol, estriol, or progesterone at concentrations ranging from 1 to 1000 nM. The cytotoxic activity of effector cells was not altered by pre-treatment of cells with steroid hormones, and the presence of the steroids in the NK assays caused minor changes only at the highest concentrations. Similarly, the effects of sera obtained from pregnant women during the third trimester and from cord blood were studied. Compared to normal pooled AB serum, pregnancy and cord sera had no effect on NK cell activity. On the contrary, the presence of fetal calf serum in the culture medium consistently resulted in a higher NK activity than that obtained with AB serum, cord serum, pregnancy serum, or the medium alone. The augmenting effect of human leukocyte interferon on NK cell activity was not inhibited by these sera. It is concluded that female sex steroid hormones and pregnancy and cord sera are not inhibitory in vitro to normal human NK cells.

Cytotoxicity, Immunologic↗

Natural killer cell activity of human fetal liver cells after allogeneic stimulation.

Cells isolated from the liver of human fetuses were confronted with mitomycin C-treated adult allogeneic cells. After this mixed leukocyte culture (MLC)-type reaction, the cytotoxic activity of fetal cells was tested against K562 cell line in a 4-h 51Cr release assay. Three of the seven fetuses tested (8 to 11 weeks of gestational age) expressed marginal cytotoxic activity before cultivation. Cells from one 8-week-old and one 9-week-old fetus were slightly more cytotoxic when cultured in the presence of allogeneic cells than when cultured in the medium only. Production of gamma interferon (IFN-gamma) was not detected in these cultures. Cells of one 18-week-old fetus expressed strong cytotoxic activity against K562 cells after MLC. Thymocytes from the same fetus were not cytotoxic, either before or after MLC against K562 cells. The results indicate that the 'prethymic' human liver contains cytotoxic cells able to spontaneously kill natural killer (NK)-sensitive target cells. Generation of strong NK-like cytotoxicity from noncytotoxic precursor cells was observed only after the thymus becomes lymphoid, suggesting that thymus-processed cells may regulate the generation of NK-like cytotoxic activity. The results suggest a different ontogeny of spontaneous and MLC-induced NK-like cells in the human fetus.

Cell Division↗

Development of natural killer cell function in the human fetus.

NK cell activity of four human premature infants between 28 and 33 wk of gestation and eleven human fetuses at 9 to 22 wk of gestation was tested against the K-562 cell line in a 4-hr 51Cr-release assay. Cord blood lymphocytes from premature infants expressed well-developed NK capacity, although the level of cytotoxicity was lower than that of full-term newborns or adults. Cells prepared from fetal liver displayed cytotoxicity against K-562 targets in four out of eleven fetuses, whereas cells from fetal bone marrow, spleen, and thymus expressed only marginal or negative anti-K-562 killing. NK cell activity in the fetal liver was observed as early as at 9 wk of gestation. The functional NK capacity of premature infants and fetuses was augmented in vitro by IFN-alpha treatment. Fetal cells without spontaneous NK activity did not develop cytotoxicity against K-562 target cells in the presence of IFN-alpha. The present results corroborate the concept of the intrauterine development of human NK cell activity.

Female↗

Natural killer cell activity in atopic dermatitis.

Natural killer (NK) cell activity against K562 cells was studied in 12 male adults with atopic dermatitis (AD). In a 4-h chromium release microcytotoxicity assay normal NK cell function and its augmentation by interferon (IFN-alpha) were observed in AD patients. Slightly higher NK cell activity was observed in patients with allergic respiratory symptoms. The role of NK cells in the pathogenesis of atopic dermatitis is discussed.

Adolescent↗

Natural killer cell function of human neonatal lymphocytes.

Human natural killer cell (NK cell) activity against K-562 target cell line was evaluated in full term cord blood (n = 30) and adult peripheral blood (n = 20) using 51Cr release assay. The level of NK cell activity was lower in cord blood compared to adult controls (39.6 +/- 11.4% vs 27.4 +/- 11.8% at effector:target ratio 50:1). Adult males showed a significantly higher NK activity compared to females. No sex difference was observed in cord blood. Furthermore, partially purified human leucocyte interferon (IFN alpha) increased in vitro NK cell function of both adult and newborn lymphocytes. The present results indicate that the appearance and maturation of human NK cells occurs during the intrauterine life of the human fetus.

Adult↗

Peptic ulcer and Helicobacter pylori in patients with lichen planus.

The aetiology of lichen planus is unknown, but it is often connected with infections. In recent years peptic ulcer disease has also been closely linked with an infectious agent, Helicobacter pylori. A case-control study was conducted in 78 patients with lichen planus to find out a previous history of peptic ulcer disease, using a questionnaire and a medical record review. Patients were also asked about family history in first- and second-degree relatives. Fifty-seven patients with other skin diseases were interviewed as controls. The prevalence of H. pylori infection in patients with lichen planus was compared to that of 39 patients with other skin diseases and to the overall prevalence rates of H. pylori infection in Finland. Our findings are consistent with an approximately three-fold increased risk of peptic ulcer in patients with chronic/repeating lichen planus, when compared to the control patients (p = 0.04) and also to the overall peptic ulcer prevalence rates in Finland. Forty-one percent of the patients with chronic/repeating lichen planus had a first- or second-degree family member with a peptic ulcer, while the corresponding rate in the control group was only 12% (p=0.003). The prevalence of H. pylori infection in patients with chronic/repeating lichen planus and transient lichen planus was not significantly different from that in patients with other skin diseases.

Adult↗

Prevalence of Sindbis-related (Pogosta) virus infections in patients with arthritis.

OBJECTIVE: To determine the role of Pogosta virus as a triggering infection in non-specific arthritis. METHODS: Serum samples of 142 patients with acute arthritis were screened for the evidence of Pogosta virus infection. Serological tests for Chlamydia trachomatis, salmonella, parvovirus B19, and Borrelia burgdorferi were also carried out. As verified later, 78 of the patients had rheumatoid arthritis and 63 seronegative poly- or oligoarthritis, while one had systemic lupus erythematosus. RESULTS: In the early stage of the joint symptoms 4 patients with rheumatoid arthritis, 1 with seronegative polyarthritis and 1 with systemic lupus erythematosus had recent Pogosta virus infection. Four of them had probably had Pogosta disease at the time of the onset of arthritis. In 11 patients with a diagnosis of seronegative arthritis, serological evidence of preceding infection due to salmonella or Chlamydia trachomatis was found, strongly suggesting classical reactive arthritis in these cases. CONCLUSIONS: Our study suggests that also a Sindbis virus infection may be associated both to an acute joint inflammation as a part of Pogosta disease or chronic arthritis. At present, this possibility still needs further research.

Adolescent↗

Antibodies to streptococcal cell wall in psoriatic arthritis and cutaneous psoriasis.

OBJECTIVE: To evaluate the possible role of streptococcal cell wall antigens in the development of psoriatic arthritis. METHODS: IgM, IgA and IgG class serum antibodies against peptidoglycan-polysaccharide (PG-PS) and peptidoglycan (PG), both from group A streptococcus, were measured in patients with psoriatic arthritis (PA), non-arthritic psoriasis (NAP), rheumatoid arthritis (RA) and in healthy controls, using ELISA. RESULTS: Both groups of psoriatic patients had elevated IgA levels specific to streptococcal PG-PS. No association with the severity of the skin disease or with the different subsets of PA was detected. Higher concentrations of IgG against the two streptococcal preparations was observed in PA than in RA. Analysis of antibody levels in patients with recent onset arthritis showed lower concentrations of IgM antibodies against streptococcal as well as control antigens in early than in late PA, whereas an overall increase of specific IgA and IgG antibodies was observed in early RA. CONCLUSION: The results suggest chronic mucosal stimulation of lymphocytes by long-lived streptococcal antigens in patients with psoriasis, without any difference observed between PA and NAP. The differences between recent onset versus established PA and RA could reflect a distinct immunopathology in the two arthritides.

Adult↗

Enterobacterial antibodies in Chinese patients with rheumatoid arthritis and ankylosing spondylitis.

OBJECTIVE: To study the role of microbial infection in rheumatic diseases. METHODS: Sera from 39 Chinese patients with rheumatoid arthritis (RA), 52 patients with ankylosing spondylitis (AS) and 51 healthy subjects (HS) were examined for IgG, IgA, and IgM class antibodies against Proteus mirabilis, Escherichia coli, Campylobacter jejuni, Salmonella typhimurium and enteritidis, Yersinia enterocolitica, and Klebsiella pneumoniae (capsular serotypes 31 and 43), using an enzyme-linked immunosorbent assay. RESULTS: In patients with RA, IgA class antibodies against all bacterial strains used as the antigen were increased when compared to healthy controls. In patients with AS, significantly elevated IgA levels were observed against Campylobacter and Klebsiella K43. IgM class antibodies were less frequently elevated in RA and in AS than IgA class antibodies. In RA patients, IgG antibodies against Klebsiella K43 and Proteus were significantly increased. No differences were observed in IgG class antibodies between AS patients and healthy controls. CONCLUSION: Increases in serum bacterial antibodies in RA and AS suggest that in both diseases stimulation of the intestinal immune system by enterobacteria may have a role. However, the question whether this phenomenon is due to increased intestinal permeability and/or represents cross reactions between different enterobacteria remains open.

Antibodies, Bacterial↗