Conjunctival interleukin-13 expression in mucous membrane pemphigoid and functional effects of interleukin-13 on conjunctival fibroblasts in vitro.
Interleukin-13 (IL-13) is the dominant effector cytokine of fibrosis in pulmonary and liver disease. Excessive conjunctival fibrosis in the immunobullous disease ocular mucous membrane pemphigoid (MMP) causes blindness; the pathogenesis of scarring in this disease is incompletely understood. To determine whether IL-13 is involved in conjunctival fibrosis in MMP, we studied the expression of IL-13 in ocular MMP patients before and after systemic immunosuppression and examined the effects of IL-13 on normal human conjunctival fibroblasts. We found high stromal cell expression of IL-13 in active ocular MMP by immunohistochemistry; 80% of these cells were CD3-positive T cells. Following immunosuppression, in clinically uninflamed, treated, ocular MMP patients, the number of IL-13 positive cells was significantly reduced, but this was still fourfold greater than in normal conjunctiva. IL-13 stimulated collagen lattice contraction and migration, and decreased production of mmp-3 and mmp-10 by human conjunctival fibroblasts. The addition of T cell culture supernatant to IL-13 synergistically augmented fibroblast migration. IL-13 also up-regulated surface expression of HLA-DR, CD80, CD40, and CD154 by conjunctival fibroblasts, suggesting a potential mechanism for fibroblast-T cell cross talk, via which fibroblasts may actively engage in perpetuating chronic inflammation and continued fibrosis. Together, these findings suggest that IL-13 is involved in conjunctival fibrosis in MMP, and that IL-13 has both profibrotic and pro-inflammatory effects on human conjunctival fibroblasts.
Saw
Valerie P J
VP
Department of Ocular Biology and Therapeutics, University College London Institute of Ophthalmology, London, United Kingdom. v.saw@ucl.ac.uk
Offiah
Ifeoma
I
Dart
Robin J
RJ
Galatowicz
Grazyna
G
Dart
John K G
JK
Daniels
Julie T
JT
Calder
Virginia L
VL
D000368:Aged; D000369:Aged, 80 and over; D054443:Cell Migration Assays; D002469:Cell Separation; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D003228:Conjunctiva / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D018793:Interleukin-13 / Q000096:biosynthesis* / Q000276:immunology; D008297:Male; D020782:Matrix Metalloproteinases / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D010390:Pemphigoid, Benign Mucous Membrane / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology
D018793:Interleukin-13; D003094:Collagen; D020782:Matrix Metalloproteinases