PMID- 33343522 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201222 IS - 1664-302X (Print) IS - 1664-302X (Electronic) IS - 1664-302X (Linking) VI - 11 DP - 2020 TI - Chlamydia psittaci Plasmid-Encoded CPSIT_P7 Elicits Inflammatory Response in Human Monocytes via TLR4/Mal/MyD88/NF-kappaB Signaling Pathway. PG - 578009 LID - 10.3389/fmicb.2020.578009 [doi] LID - 578009 AB - The chlamydial plasmid, an essential virulence factor, encodes plasmid proteins that play important roles in chlamydial infection and the corresponding immune response. However, the virulence factors and the molecular mechanisms of Chlamydia psittaci are not well understood. In the present study, we investigated the roles and mechanisms of the plasmid-encoded protein CPSIT_P7 of C. psittaci in regulating the inflammatory response in THP-1 cells (human monocytic leukemia cell line). Based on cytokine arrays, CPSIT_P7 induces the expression of interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1) in THP-1 cells. Moreover, the expression levels of IL-6, IL-8, and MCP-1 stimulated by CPSIT_P7 declined after silencing of the Toll-like receptor 4 (TLR4) gene using small interfering RNA and transfection of a dominant negative plasmid encoding TLR4 (pZERO-hTLR4). We further demonstrated that transfection with the dominant negative plasmid encoding MyD88 (pDeNy-hMyD88) and the dominant negative plasmid encoding Mal (pDeNy-hMal) could also abrogate the expression of the corresponding proteins. Western blot and immunofluorescence assay results showed that CPSIT_P7 could activate nuclear factor kappaB (NF-kappaB) signaling pathways in THP-1 cells. Altogether, our results indicate that the CPSIT_P7 induces the TLR4/Mal/MyD88/NF-kappaB signaling axis and therefore contributes to the inflammatory cytokine response. CI - Copyright (c) 2020 Chen, Li, Yan, Sun, Wang, Liu, Xiao, Lu and Wu. FAU - Chen, Qian AU - Chen Q AD - Institution of Pathogenic Biology, Hengyang Medical College, University of South China, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China. AD - Institute of Clinical Research, The First Affiliated Hospital of University of South China, Hengyang, China. FAU - Li, Yumeng AU - Li Y AD - Institution of Pathogenic Biology, Hengyang Medical College, University of South China, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China. AD - Department of Clinical Laboratory, The First Affiliated Hospital of University of South China, Hengyang, China. FAU - Yan, Xiaoliang AU - Yan X AD - Institution of Pathogenic Biology, Hengyang Medical College, University of South China, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China. FAU - Sun, Zhenjie AU - Sun Z AD - Institution of Pathogenic Biology, Hengyang Medical College, University of South China, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China. FAU - Wang, Chuan AU - Wang C AD - Institution of Pathogenic Biology, Hengyang Medical College, University of South China, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China. FAU - Liu, Shuangquan AU - Liu S AD - Department of Clinical Laboratory, The First Affiliated Hospital of University of South China, Hengyang, China. FAU - Xiao, Jian AU - Xiao J AD - Institution of Pathogenic Biology, Hengyang Medical College, University of South China, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China. FAU - Lu, Chunxue AU - Lu C AD - Institution of Pathogenic Biology, Hengyang Medical College, University of South China, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China. FAU - Wu, Yimou AU - Wu Y AD - Institution of Pathogenic Biology, Hengyang Medical College, University of South China, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China. LA - eng PT - Journal Article DEP - 20201203 PL - Switzerland TA - Front Microbiol JT - Frontiers in microbiology JID - 101548977 PMC - PMC7744487 OTO - NOTNLM OT - CPSIT_P7 OT - Chlamydia psittaci OT - TLR4 OT - human monocytes OT - inflammation COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2020/12/22 06:00 MHDA- 2020/12/22 06:01 PMCR- 2020/12/03 CRDT- 2020/12/21 06:04 PHST- 2020/07/19 00:00 [received] PHST- 2020/10/29 00:00 [accepted] PHST- 2020/12/21 06:04 [entrez] PHST- 2020/12/22 06:00 [pubmed] PHST- 2020/12/22 06:01 [medline] PHST- 2020/12/03 00:00 [pmc-release] AID - 10.3389/fmicb.2020.578009 [doi] PST - epublish SO - Front Microbiol. 2020 Dec 3;11:578009. doi: 10.3389/fmicb.2020.578009. eCollection 2020.