While MMPs are required for normal tissue homeostasis, there is also evidence that they play a role in the pathogenesis

of a range of inflammatory-fibrotic Bcr-Abl inhibitor diseases [84], [85] and [86], disrupting the basement membrane and aiding the recruitment of inflammatory cells [87]. MMPs have wide-ranging effects on inflammatory and immune processes, such as modulating chemokine activity and activation of TGFβ, IL-1β and TNF [88]. They are known to be important in a number of ocular surface diseases, and inhibition of MMP activity has been shown to reduce conjunctival scarring after glaucoma surgery [89]. MMP9 is part of the neutrophil lysosome, and mediates epithelial dissolution through degradation of type IV collagen [82]. Children with active trachoma have increased amounts of conjunctival MMP9 (determined by immunohistochemistry, zymography and gene expression analysis) [46] and [90]. Scarring trachoma is associated with increased expression of MMP9 and a coding SNP that is adjacent to the active binding site of the MMP9 enzyme [46], [68] and [91], and with differential expression of MMPs 7, 9, 10 and 12 and tissue inhibitor of MMP (TIMP)-1; recurrence of trichiasis after surgery is associated with

an altered MMP1/TIMP1 transcript ratio [55], [67], [68] and [92]. Scar tissue in trachoma probably originates from activated fibroblasts which are stimulated to produce collagen by profibrogenic check details mediators (TGF-β, PDGF, CTGF and bFGF) [50], [93] and [94]. Chemokines have also been shown to act as fibrogenic mediators, in particular, the CC- and CXC-chemokine families, and various members of these families have been associated with scarring, including the pro-fibrogenic the CCL18 [50], [55], [69] and [87]. Since the pathology of Ct infection is similar in the eye and genital tract [4] and [16], and both are part of the common mucosal immune

system, it is likely that similar processes lead to resolution of infection and/or the development of scarring sequelae at each site. The few studies that have been conducted on the immunological correlates of protective immunity and immunopathology in human genital Ct infection have reached broadly similar conclusions to those of studies in the eye [10], [95], [96] and [97]. Local, endocervical IgA antibodies appear to be protective [95], and stronger Th-1 type cell-mediated immune responses to Ct antigens are seen in the peripheral blood of subjects who do not have sequelae [96] and [97]. An important difference between ocular and genital infection is that in the eye, the damaging sequelae occur at the site of the initial infection, the conjunctival epithelium. By contrast, in the female genital tract the major sequelae develop in the fallopian tubes and not at the cervix, which is the site of inoculation. Impairment of immunological barriers to ascending infection may explain the association between HIV infection and chlamydial PID [98]; no association has been reported between HIV and trachoma.