Actually there was more attention to

Actually, there was more attention to the effect of CsA on GO that have been clearly demonstrated. Hence, in this investigation we tried also to focus on TAC as well. To our knowledge this comparative immune-histochemical investigation using this group of cytokines has been not previously attempted especially among liver transplant recipients with exclusion of other allograft recipients such as renal transplant recipients, based on previous studies that have been clearly demonstrated that calcium channel blockers concurrently used by those patients more specifically nifedipine, usually presented more sever GO, thus potentiating the effect of CsA or TAC on the gingival tissue [31,10]. It is well known that healthy gingiva is in a continuous state of wound repair (cell/tissue turnover) due to constant insult from bacterial plaque, in which growth factors may play an important role in this reparative or maintenance process. Within this scenario, it would be expected to find one or more of the growth factors with wound repair in normal gingiva. Consequently it might also be expected to find an elevated level or even an increased number of growth factors in conditions which involve increased tissue volume such as drug-induced gingival overgrowth and HGF [32]. Obviously, it is likely that a complex interaction between several growth factors/cytokines contributes to the clinical presentations of GO. Although it would be simpler if the drug-induced tissue response and HGF were specific in nature. Therefore in our study we selected a group of growth factors and cytokines suspecting their role in collagen turnover maintenance, either by enhancing fibroblast proliferation and ECM accumulation represented by TGF- β1and PDGF-B or by controlling the matrix degradation through the action of MMP-9 produced by fibroblast as well as TIMP-1. Additionally, we have not investigated the possible changes in PDGF-A chain or TGF- β3. As it does not play a major role in GSK-J1 sodium salt proliferation [33,14]. The number of subjects participating in this study was quite sufficient, to provide a high level of confidence in the generality of the results obtained. With exception to the group of HGF which is consisted of two sisters and their mother, indeed we were lucky to find three relatives as these cases are very rare. All subjects in the group of DIGO and control group were males as progesterone decrease glycosaminoglycan synthesis by human gingival fibroblasts and suppress GO [34]. In the present work, all tissue samples were harvested after complete subsidence of inflammation, as inflammatory process induces alterations in the expression of growth factors and potentially modifies tissue response [35]. In our work, the histopathological results of HGF cases consistent with the studies of Araujo et al., and Doufexi et al., [36,37]. The data showed hyperplasia of a dense hyperkeratotic epithelium with elongated rete pegs that penetrate deep in the connective tissue. The connective tissue in HGF exhibits an accumulation of excess collagen, as well as elastic and oxytalan fibers, the collagen fibers are typically organized as thick parallel fiber bundles that are clearly detected by Masson Trichrome stain showing deep stain when compared to DIGO group. Meanwhile, the results of immune-histochemical investigation of gingival tissue samples of HGF group and CsA group showed significantly higher diffuse expression of TGF-β1 and PDGF-B, when compared to TAC group and control one. As in TAC and control groups the expression of TGF-β1 and PDGF-B is considered focal expression. This focal expression of TGF-β1 in TAC group is consistent with the previous studies of Mohammed et al., and [38,39]. Also, the diffuse expression of TGF-β1 and PDGF-B in CsA group confirms previous investigations done by Plemons et al., Nares et al., and Duncan et al., [25,30,40,41]. In addition, Wright et al., they confirmed the diffuse expression of TGF-β1 in HGF samples. The results showed a diffuse expression of MMP-9 in CsA group and TAC group when compared to focal expression of HGF and control groups. These data are consistent with the studies of Gagliano et al., and [42,2] their data showed significant expression of MMP-1 in human gingival fibroblast treated with CsA or TAC. As regard the expression of TIMP-1, data demonstrated a significant diffuse expression in HGF group when compared to DIGO group and control.