| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1From the Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts; and the 2Department of Ophthalmology, Immunology and Uveitis Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts.
PURPOSE. Macrophage migration inhibitory factor (MIF) is a pleiotropic, proinflammatory cytokine that mediates various immunoinflammatory processes. Ocular cicatricial pemphigoid (OCP) is an autoimmune disease in which affected conjunctivae show features of an immunoinflammatory disease. In this study, the role of MIF in the pathogenesis of OCP was examined.
METHODS. The expression of MIF in conjunctival tissues of patients with OCP (n = 10) and normal subjects (n = 5) was studied by quantitative real-time PCR and immunohistochemistry. The production of MIF by conjunctival fibroblasts of normal control subjects and patients with OCP was determined, by using quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA). In addition, the effects of interleukin (IL)-1, tumor necrosis factor (TNF)-
, and transforming growth factor (TGF)-ß1 on the induction of MIF by conjunctival fibroblasts were studied by quantitative real-time PCR. To determine the relationship between conjunctival expression of MIF and accumulation of macrophages, in patients with OCP, a correlation study was performed.
RESULTS. An increased conjunctival expression of MIF was detected in patients with OCP, both at the mRNA (by real-time PCR) and protein level (by immunohistochemistry), compared with normal control patients. The expression of MIF was detected in the epithelial cells and occasionally in the stromal cells in control conjunctival tissues, by immunohistochemistry. In contrast, a statistically significant increase (P < 0.0001) in the expression of MIF was detected in the stromal cells of conjunctival tissues obtained from patients with OCP (control: 4.89 ± 0.5; OCP: 19.82 ± 1.34). By quantitative real-time PCR, compared with control conjunctiva, an increase in the expression of MIF was detected in the conjunctiva obtained from patients with OCP. A similar increase in the expression of MIF was also detected in conjunctival fibroblasts of patients with OCP, compared with control fibroblasts, by quantitative real-time PCR. A significantly increased (P < 0.001) level of MIF was also detected in supernatant collected from conjunctival fibroblasts of patients with OCP (186 ± 5.4), compared with supernatant collected from control fibroblasts (9.3 ± 7.6). Moreover, IL-1, TNF-, and TGF-ß1, known factors involved in the pathogenesis of OCP, were found to induce the expression of MIF by conjunctival fibroblasts. A statistically significant correlation (P < 0.0001, r2 = 0.4465) was observed between the expression of MIF and accumulation of CD68-positive macrophages in conjunctiva of patients with OCP.
CONCLUSIONS. This study demonstrated an increased conjunctival expression of MIF in patients with OCP. MIF may be actively involved in the pathogenesis of OCP, possibly regulating the inflammatory events of the disease process.
This article has been cited by other articles:
|
|
 |
|
  S. Yamagami, S. Yokoo, S. Amano, and N. Ebihara Characterization of Bone Marrow Derived Cells in the Substantia Propria of the Human Conjunctiva Invest. Ophthalmol. Vis. Sci., October 1, 2007; 48(10): 4476 - 4481. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Canizares, D. I. Smith, M. S. Conners, K. J. Maverick, and M. P. Heffernan Successful treatment of mucous membrane pemphigoid with etanercept in 3 patients. Arch Dermatol, November 1, 2006; 142(11): 1457 - 1461. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. Heffernan and D. D. Bentley Successful treatment of mucous membrane pemphigoid with infliximab. Arch Dermatol, October 1, 2006; 142(10): 1268 - 1270. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
