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Int J Med Sci 2017; 14(5):484-493. doi:10.7150/ijms.18059 This issue Cite

Research Paper

Effects of C-reactive protein on the expression of matrix metalloproteinases and their inhibitors via Fcγ receptors on 3T3-L1 adipocytes

Kumiko Nakai^{1, 2}, Hideki Tanaka^{1, 2}, Kazuhiro Yamanaka¹, Yumi Takahashi³, Fumiko Murakami³, Rieko Matsuike³, Jumpei Sekino³, Natsuko Tanabe^{2, 4}, Toyoko Morita^{1, 5}, Yoji Yamazaki⁵, Takayuki Kawato^{1, 2✉}, Masao Maeno^{1, 2}

1. Department of Oral Health Sciences, Nihon University School of Dentistry, Tokyo, Japan;
2. Division of Functional Morphology, Dental Research Center, Nihon University School of Dentistry, Tokyo, Japan;
3. Nihon University Graduate School of Dentistry, Tokyo, Japan;
4. Department of Biochemistry, Nihon University School of Dentistry, Tokyo, Japan;
5. The Lion Foundation for Dental Health, Tokyo, Japan.

✉ Corresponding author: Takayuki Kawato, DDS, PhD., Department of Oral Health Sciences, Nihon University School of Dentistry, 1-8-13, Kanda Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan Tel.: +81-3-3219-8128; Fax: +81-3-3219-8138. E-mail: kawato.takakyukiac.jp More

Abstract

The association between obesity and inflammation is well documented in epidemiological studies. Proteolysis of extracellular matrix (ECM) proteins is involved in adipose tissue enlargement, and matrix metalloproteinases (MMPs) collectively cleave all ECM proteins. Here, we examined the effects of C-reactive protein (CRP), an inflammatory biomarker, on the expression of MMPs and tissue inhibitors of metalloproteinases (TIMPs), which are natural inhibitors of MMPs, in adipocyte-differentiated 3T3-L1 cells. We analyzed the expression of Fcγ receptor (FcγR) IIb and FcγRIII, which are candidates for CRP receptors, and the effects of anti-CD16/CD32 antibodies, which can act as FcγRII and FcγRIII blockers on CRP-induced alteration of MMP and TIMP expression. Moreover, we examined the effects of CRP on the activation of mitogen-activated protein kinase (MAPK) signaling, which is involved in MMP and TIMP expression, in the presence or absence of anti-CD16/CD32 antibodies. Stimulation with CRP increased MMP-1, MMP-3, MMP-9, MMP-11, MMP-14, and TIMP-1 expression but did not affect MMP-2, TIMP-2, and TIMP-4 expression; TIMP-3 expression was not detected. Adipocyte-differentiated 3T3-L1cells expressed FcγRIIb and FcγRIII; this expression was upregulated on stimulation with CRP. Anti-CD16/CD32 antibodies inhibited CRP-induced expression of MMPs, except MMP-11, and TIMP-1. CRP induced the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 and p38 MAPK but did not affect SAPK/JNK phosphorylation, and Anti-CD16/CD32 attenuated the CRP-induced phosphorylation of p38 MAPK, but not that of ERK1/2. These results suggest that CRP facilitates ECM turnover in adipose tissue by increasing the production of multiple MMPs and TIMP-1 in adipocytes. Moreover, FcγRIIb and FcγRIII are involved in the CRP-induced expression of MMPs and TIMP-1 and the CRP-induced phosphorylation of p38, whereas the FcγR-independent pathway may regulate the CRP-induced MMP-11 expression and the CRP-induced ERK1/2 phosphorylation.

Keywords: 3T3-L1 adipocyte, C-reactive protein, extracellular matrix, Fcγ receptor, matrix metalloproteinase, tissue inhibitor of metalloproteinase.

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