Human leukocyte histocompatibility antigen class II‐induced cytokines from human gingival fibroblasts promote proliferation of human umbilical vein endothelial cells: potential association with enhanced angiogenesis in chronic periodontal inflammation

Abstract

The HLA-II-induced IL-8, via CXCR1, as well as MCP-1 from GF, promotes endothelial cell proliferation, which is possibly associated with enhanced angiogenesis in chronic periodontal lesions.

Antibodies in Transplantation: The Effects of HLA and Non-HLA Antibody Binding and Mechanisms of Injury

“…Cells become activated and proliferate or undergo apoptosis depending on which intracellular pathway is predominantly activated [120–122]. Fibroblasts stimulated through HLA II increase production of prostaglandin E [123], RANTES, interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, and GROα [124, 125], through Janus kinase (JNK) and FAK signaling [126]. These HLA II-induced soluble factors produced by fibroblasts could promote proliferation of endothelial cells [124].…”

Fibroblasts stimulated via HLA-II molecules produce prostaglandin E2 and regulate cytokine production from helper T cells

“…Previously, we reported that fibroblasts produce several cytokines such as RANTES, MCP-1, IL-6, IL-8, and the growth-related gene product following HLA-II stimulation. 11,18 These results suggested that fibroblasts stimulated thus might act in the recruitment of immunological cells and angiogenesis at sites of inflammatory lesions. Accordingly, this study estimated the effects of soluble factors from HLA-II-stimulated fibroblasts on the immunological responses mediated by Th cells.…”

“…There was little difference in the total amounts of these cytokines between DR-sup and DQ-sup in each HGF donor cell line tested in this study. However, no difference was detected in the profile of cytokines secreted by HGF stimulated via HLA-DR or -DQ molecules according to our commercially supplied cytokine array (Raibiotech, Norcross, GA, USA) 18 (data not shown). Naïve T cells co-cultured with allogeneic DCs in the presence of HGF culture supernatant from DQ-sup-stimulated, but not DR-sup-stimulated cells differentiated into cells able to produce high amounts of Th2-type cytokines, including IL-5 and IL-13, as compared with the Th1 cytokine, IFN-g (Figure 2a).…”

“…18 As PGE 2 was recently implicated in promoting Th2 polarization in Th cells, 22,23 we next compared PGE 2 production between HGF stimulated via HLA-DR and -DQ. Surprisingly, PGE 2 was detected only in DQ-sup, but neither in DR-sup nor in the culture supernatant of HGF without stimulus, whereas the levels of secreted RANTES and MCP-1 did not differ between stimuli (Figure 3).…”

Distinct phenotype and therapeutic potential of gingival fibroblasts

“…This may, at least in part, depend on the distinct phenotype of gingival cells (Table II). Gingival fibroblasts secrete proangiogenic vascular endothelial growth factor (VEGF), CXCL12 (stromal cellederived factor-1a), CXCL8 (IL-8), CCL2 (monocyte chemoattractant protein-1), and CXCR1, and promote endothelial cell growth in vitro (51,94,95), but the relevance of this for angiogenesis in vivo or in in vitro models is not known. Gingival fibroblasts also produce abundantly factors that promote re-epithelialization, including keratinocyte growth factor (FGF7) and hepatocyte growth factor/scatter factor (HGF/SF) (96).…”