Treponema pallidum recombinant protein Tp47 enhanced interleukin-6 secretion in human dermal fibroblasts through the toll-like receptor 2 via the p38, PI3K/Akt,and NF-κB signalling pathways |
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| Affiliation: | 1. Center of Clinical Laboratory, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, China;2. Department of Clinical Laboratory, Weifang People''s Hospital, Weifang, Shandong 261000, China;3. Department of Medical Laboratory, The Second Affiliated Hospital of Xiamen Medical College, Xiamen 361004, China;4. Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen 361004, China;1. Department of Biochemistry and Molecular Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China;2. Guizhou Prenatal Diagnosis Center, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou, China;3. Department of Clinical Biochemistry, School of Medical Laboratory Science, Guizhou Medical University, Guiyang 550004, Guizhou, China;1. College of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, PR China;2. State Key Laboratory of Trauma, Burns and Combined Injury, Daping Hospital, Army Medical University, Chongqing 400042, PR China;1. Department of Medical Cosmetology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China;2. Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China;3. Department of Plastic Surgery, China-Japan Friendship Hospital, Beijing 100029, China;1. Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw 02-106, Poland;2. Life Sciences Institute, Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA |
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| Abstract: | Interleukin-6 (IL-6) is a multi-effective cytokine involved in multiple immune responses. Whether fibroblasts also turn out to be a cytokine IL-6 factory during interaction with Treponema pallidum is not yet understood. To explore whether fibroblasts participate in inflammation due to syphilis, a series of experiments were performed to explore the role of T. pallidum lipoprotein Tp47 in IL-6 production in human dermal fibroblasts. The Toll-like receptor 2 (TLR2) and participating signalling pathways in this process were also evaluated. The results showed that the expressions of IL-6 and the protein levels of TLR2 in fibroblasts were upregulated after stimulation with Tp47, and this effect was impeded by the TLR2 inhibitor C29. In addition, Tp47 promoted the phosphorylation of p38, PI3K/Akt, and nuclear factor-kappaB (NF-κB), and the translocation of NF-κB in fibroblasts. Moreover, p38, PI3K, and NF-κB inhibitors significantly reduced IL-6 production in fibroblasts stimulated with Tp47. Furthermore, the TLR2 inhibitor C29 inhibited the phosphorylation of p38, Akt, and NF-κB, and the translocation of NF-κB in fibroblasts. In conclusion, our results showed that Tp47 enhanced IL-6 secretion in human dermal fibroblasts through TLR2 via p38, PI3K/Akt, and NF-κB signalling pathways. These findings contribute to our understanding of syphilis inflammation. |
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