Oncostatin M synergistically induces CXCL10 and ICAM-1 expression in IL-1beta-stimulated-human gingival fibroblasts.
Periodontitis is a chronic bacterial infection of tooth-supporting structures. T-helper type 1 (Th1) cells are related to the exacerbation of periodontal disease. Human gingival fibroblasts (HGFs), the major cell type in periodontal connective tissues, are involved in immunological response in periodontal tissues. However, it is uncertain whether HGFs are related to Th1 response. Chemokine (C-X-C motif) ligand 10 (CXCL10) is a cytokine, that is related to Th1 cells migration. Intercellular adhesion molecule (ICAM)-1 is involved in Th1 cells retention and activation in inflamed tissue. The aim of this study is to examine the effect of oncostatin M (OSM) on CXCL10 and ICAM-1 expression in HGFs. OSM stimulation induced CXCL10 and ICAM-1 expression in HGFs. Moreover, the synergistic effects of CXCL10 release and ICAM-1 expression in HGFs were observed with combined stimulation of interleukin (IL)-1beta and OSM. OSM increased type 1 IL-1 receptor (IL-1R1) expression, and IL-1beta enhanced OSMRbeta expression on HGFs. IL-1beta + OSM stimulation enhanced the phosphorylation of inhibitor of nuclear factor kappaB (IkappaB)-alpha, signal transducer and activator of transcription (STAT)3, c-Jun N terminal kinase (JNK), and protein kinase B (Akt) compared to OSM or IL-1beta stimulation. CXCL10 production from OSM + IL-1beta stimulated HGFs was suppressed by nuclear factor (NF)-kappaB, STAT3, JNK, and phosphoinositide-3-kinase (PI3K) inhibitors. On the other hand, only NF-kappaB and STAT3 inhibitors suppressed ICAM-1 expression enhanced by OSM + IL-1beta treatment. These effects of OSM and IL-1beta may promote Th1 cells infiltration and retention in periodontally diseased tissues and be related to exacerbation of periodontal disease.
Hosokawa
Yoshitaka
Y
Department of Conservative Dentistry, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan. hosokawa@dent.tokushima-u.ac.jp
Hosokawa
Ikuko
I
Ozaki
Kazumi
K
Nakae
Hideaki
H
Matsuo
Takashi
T
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000276:immunology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D005881:Gingiva / Q000166:cytology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D053583:Interleukin-1beta / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology; D053683:Oncostatin M / Q000494:pharmacology*; D010518:Periodontitis / Q000276:immunology; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology
D000970:Antineoplastic Agents; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D053583:Interleukin-1beta; D016328:NF-kappa B; D053683:Oncostatin M; D018799:Intercellular Adhesion Molecule-1; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases