Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.4 (ribonuclease)
6,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aqueous humor (AqH) contains immunosuppressive factors, especially TGF-beta2, that contribute to the immune privileged status of the anterior chamber. However, this may not be true when the blood-ocular barrier is compromised by ocular inflammation. To determine the immunosuppressive status of AqH from murine eyes afflicted with experimental autoimmune uveitis, B10.A mice were immunized with interphotoreceptor retinoid-binding protein. AqH was collected from eyes of affected mice periodically after immunization and then evaluated for content of TGF-beta, proinflammatory cytokines, and the capacity to suppress anti-CD3-driven T cell proliferation. mRNA expression of selected cytokines in iris and ciliary body from inflamed eyes was analyzed by ribonuclease protection assay. We found that TGF-beta levels were significantly increased in AqH from EAU eyes on days 11, 17, and 28. AqH collected on day 11 (onset of disease) failed to suppress T cell proliferation and contained large amounts of locally produced IL-6 that antagonized TGF-beta. In contrast, AqH collected at 17 days (when ocular inflammation was progressively severe) re-expressed the ability to suppress T cell proliferation, in this case due to high levels of blood-derived TGF-beta1 and eye-derived TGF-beta2 in the absence of IL-6. Thus, during the onset of experimental autoimmune uveitis, the ocular microenvironment loses its immunosuppressive properties due to local production of IL-6. But as inflammation mounts, AqH IL-6 content falls, and the fluid reacquires sufficient TGF-beta eventually to suppress immunogenic inflammation. The paradoxical roles of IL-6 in antagonizing TGF-beta, while promoting TGF-beta accumulation during ocular inflammation, is discussed.
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PMID:Analysis of immunomodulatory activities of aqueous humor from eyes of mice with experimental autoimmune uveitis. 1064 Jul 29

Uveitis is an inflammation of the uveal tract and is one of the major causes of visual impairment. Several lines of evidence suggest an important role for activated T lymphocytes in the perpetuation of posterior uveitis. In sequel to our preliminary observations with human S-antigen, we have further investigated the proliferative response of peripheral blood lymphocytes of posterior uveitis patients against 20 linear and 9 overlapping peptides of retinal S-antigen. The expression of surface markers CD4, CD8, CD29, CD45RA in peripheral blood was detected by flow cytometry. We have also assessed the pattern of cytokines present in peripheral blood mononuclear cells (PBMCs) using ribonuclease protection assay (RPA). Nineteen out of 32 patients' lymphocytes showed proliferative response to S-antigen, one or more of its 20 linear and nine overlapping synthetic peptides. Six patients showed significant lymphoproliferative response against various peptides. The maximum response was found to peptides from the 231-270 amino acid region of human S-antigen sequence. The percentage of CD29(+) (memory cells) and CD45RA(+) (naive cells) T-lymphocytes was higher in patients compared to healthy volunteers. There was a demonstrable difference in the percentage of CD4(+) and CD8(+) lymphocytes in the patients (P <== 0.05) as compared to controls. Higher message for interleukin (IL)-5, IL-10, IL-15, IL-9, IL-2, IL-13, and interferon (IFN)-gamma was observed in uveitis patients than in healthy individuals. In brief, our study suggests that a particular region of S-antigen plays an important role in idiopathic uveitis.
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PMID:Human S-antigen: peptide determinant recognition in uveitis patients. 1501 Feb 90