PMID- 19515021 OWN - NLM STAT- MEDLINE DCOM- 20090915 LR - 20090611 IS - 1600-0765 (Electronic) IS - 0022-3484 (Linking) VI - 44 IP - 1 DP - 2009 Feb TI - 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. PG - 103-9 LID - 10.1111/j.1600-0765.2008.01097.x [doi] AB - BACKGROUND AND OBJECTIVE: The role of human leukocyte histocompatibility antigen (HLA) class II molecules on non-antigen-presenting cells has been a matter of controversy. We previously reported that HLA-II molecules on human gingival fibroblasts (GF) do not present antigens, but transduce signals into the cells, resulting in the expression of several cytokines, such as interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), regulated upon activation, normal T-cell expressed and secreted (RANTES) and IL-8. However, the exact role of these cytokines, as well as other cytokines which are potentially secreted from GF, in the pathogenesis of chronic periodontal inflammation is not fully understood. The aim of this study was to observe the effects of HLA-II-induced cytokines on the proliferation of human umbilical vein endothelial cells (HUVEC). MATERIAL AND METHODS: Antibody-based cytokine-microarray analyses were performed to detect potential cytokines associated with angiogenesis. Next, cytokine productivity was confirmed by quantitative methods. Then, cell proliferation assay was performed to see whether these cytokines promoted the proliferation of HUVEC. RESULTS: Besides IL-6, MCP-1, RANTES and IL-8, growth-related gene product (GRO) was newly identified as an HLA-II-induced cytokine released from GF. This was confirmed by a quantitative method. Cell culture supernatant from HLA-II-stimulated GF cultures promoted the growth of HUVEC. Addition of anti-IL-8 neutralizing antibody, anti-CXC receptor (CXCR)1 antibody and anti-MCP-1 antibody inhibited the growth of HUVEC in a dose-dependent manner, while addition of anti-GROalpha antibody did not. CONCLUSION: 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. FAU - Okada, Y AU - Okada Y AD - Department of Patho-physiology-Periodontal Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. FAU - Meguro, M AU - Meguro M FAU - Ohyama, H AU - Ohyama H FAU - Yoshizawa, S AU - Yoshizawa S FAU - Takeuchi-Hatanaka, K AU - Takeuchi-Hatanaka K FAU - Kato, N AU - Kato N FAU - Matsushita, S AU - Matsushita S FAU - Takashiba, S AU - Takashiba S FAU - Nishimura, F AU - Nishimura F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Periodontal Res JT - Journal of periodontal research JID - 0055107 RN - 0 (Antibodies) RN - 0 (CCL2 protein, human) RN - 0 (CXCL1 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CCL5) RN - 0 (Chemokine CXCL1) RN - 0 (Cytokines) RN - 0 (HLA-DQ Antigens) RN - 0 (HLA-DR Antigens) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (Interleukin-6) RN - 0 (Interleukin-8) RN - 0 (Receptors, Interleukin-8A) SB - IM MH - Antibodies/immunology MH - Cell Proliferation MH - Cells, Cultured MH - Chemokine CCL2/antagonists & inhibitors/immunology MH - Chemokine CCL5/immunology MH - Chemokine CXCL1/immunology MH - Chronic Periodontitis/immunology/*pathology MH - Cytokines/*immunology MH - Endothelial Cells/immunology/*pathology MH - Endothelium, Vascular/immunology/*pathology MH - Fibroblasts/*immunology MH - Gingiva/*immunology/pathology MH - HLA-DQ Antigens/immunology MH - HLA-DR Antigens/immunology MH - Histocompatibility Antigens Class II/*immunology MH - Humans MH - Interleukin-6/immunology MH - Interleukin-8/antagonists & inhibitors/immunology MH - Neovascularization, Pathologic/immunology/*pathology MH - Receptors, Interleukin-8A/antagonists & inhibitors/immunology MH - Umbilical Veins/immunology/*pathology EDAT- 2009/06/12 09:00 MHDA- 2009/09/16 06:00 CRDT- 2009/06/12 09:00 PHST- 2009/06/12 09:00 [entrez] PHST- 2009/06/12 09:00 [pubmed] PHST- 2009/09/16 06:00 [medline] AID - JRE1097 [pii] AID - 10.1111/j.1600-0765.2008.01097.x [doi] PST - ppublish SO - J Periodontal Res. 2009 Feb;44(1):103-9. doi: 10.1111/j.1600-0765.2008.01097.x.