The Type III Secretion System (T3SS) of<i>Chlamydophila psittaci</i>Is Involved in the Host Inflammatory Response by Activating the JNK/ERK Signaling Pathway

He, Qing; Zeng, Huai-cai; Huang, Yan; Yanqun, Hu; Wu, Yimou

doi:10.1155/2015/652416

Cited by 6 publications

(5 citation statements)

References 40 publications

(46 reference statements)

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“…ERK1/2 are activated by MAP/ERK1/2 kinases 1 and 2 (MEK1/2) by dual phosphorylation at their threonine 202 and tyrosine 204 residues ( Cagnol and Chambard, 2010 ). Activated ERK1/2 and SAPK/JNK can directly phosphorylate a variety of cytoplasmic and nuclear substrates involved in various cellular processes such as proliferation, differentiation, apoptosis and survival ( He et al., 2015 ; Meng et al., 2019 ; Sharma et al., 2019 ). p38 protein kinase is a tyrosine phosphoprotein kinase associated with inflammation and growth factor responses ( Mo et al., 2020 ).…”

Section: Discussionmentioning

confidence: 99%

The Hypothetical Inclusion Membrane Protein CPSIT_0846 Regulates Mitochondrial-Mediated Host Cell Apoptosis via the ERK/JNK Signaling Pathway

Tang

Chen

et al. 2021

Front. Cell. Infect. Microbiol.

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Chlamydia psittaci is an important zoonotic factor associated with human and animal atypical pneumonia. Resisting host cell apoptosis is central to sustaining Chlamydia infection in vivo. Chlamydia can secrete inclusion membrane proteins (Incs) that play important roles in their development cycle and pathogenesis. CPSIT_0846 is an Inc protein in C. psittaci identified by our team in previous work. In the current study, we investigated the regulatory role of CPSIT_0846 in HeLa cell apoptosis, and explored potential mechanisms. The results showed that HeLa cells treated with CPSIT_0846 contained fewer apoptotic bodies and exhibited a lower apoptotic rate than untreated cells either with Hoechst 33258 fluorescence staining or flow cytometry with or without induction by staurosporine (STS). CPSIT_0846 could increase the phosphorylation of the extracellular signal-regulated kinases 1/2 (ERK1/2) or stress-activated protein kinases/c-Jun amino-terminal kinases (SAPK/JNK) signaling pathways, and the Bcl-2 associated X protein (Bax)/B cell lymphoma 2 (Bcl-2) ratio, levels of cleaved caspase-3/9 and cleaved Poly-ADP-ribose polymerase (PARP) were significantly up-regulated following inhibition of ERK1/2 or SAPK/JNK pathways with U0126 or SP600125. After carbonyl cyanide 3-chlorophenylhydrazone (CCCP) treatment, the mitochondrial membrane potential (MMP) of cells was significantly decreased in control group, but stable in the CPSIT_0846 treated one, and less cytochrome c (Cyt.c) was released into the cytoplasm. Inhibition of the ERK1/2 or SAPK/JNK pathway significantly decreased the JC-1 red-green fluorescence signal, and promoted Cyt.c discharge into the cytoplasm in HeLa cells treated with CPSIT_0846. In conclusion, CPSIT_0846 can regulate mitochondrial pathway-mediated apoptosis in HeLa cells by activating the ERK/JNK signaling pathway.

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Section: Discussionmentioning

confidence: 99%

The Hypothetical Inclusion Membrane Protein CPSIT_0846 Regulates Mitochondrial-Mediated Host Cell Apoptosis via the ERK/JNK Signaling Pathway

Tang

Chen

et al. 2021

Front. Cell. Infect. Microbiol.

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“…Moreover, MAPKs can cooperate with other signal transduction pathways, including that of the transcriptional regulator nuclear factor-κβ (NF-κβ), which regulates the transcription of genes important for cytokine and chemokine production, including interleukin IL-6, IL-8, IL-12, and tumor necrosis factor-α [ 16 , 17 , 18 ], as well as the anti-apoptotic factor Bcl-2 [ 17 , 19 ]. Phosphorylation of MAPKs leads to activation or inhibition of transcription factors [ 15 , 20 ], resulting in up- or down-regulation of important immune factor genes that regulate bacterial infections in the host [ 13 , 21 , 22 , 23 , 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

Edwardsiella ictaluri T3SS Effector EseN Modulates Expression of Host Genes Involved in the Immune Response

et al. 2022

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The type III secretion system (T3SS) effector EseN is encoded on the Edwardsiella ictaluri chromosome and is homologous to a family of T3SS effector proteins with phosphothreonine lyase activity. Previously we demonstrated that E. ictaluri invasion activates extracellular signal-regulated kinases 1 and 2 (ERK1/2) early in the infection, which are subsequently inactivated by EseN. Comparative transcriptomic analysis showed a total of 753 significant differentially expressed genes in head-kidney-derived macrophages (HKDM) infected with an EseN mutant (∆EseN) compared to HKDM infected with wild-type (WT) strains. This data strongly indicates classical activation of macrophages (the M1 phenotype) in response to E. ictaluri infection and a significant role for EseN in the manipulation of this process. Our data also indicates that E. ictaluri EseN is involved in the modulation of pathways involved in the immune response to infection and expression of several transcription factors, including NF-κβ (c-rel and relB), creb3L4, socs6 and foxo3a. Regulation of transcription factors leads to regulation of proinflammatory interleukins (IL-8, IL-12a, IL-15, IL-6) and cyclooxygenase-2 (COX-2) expression. Inhibition of COX-2 mRNA by WT E. ictaluri leads to decreased production of prostaglandin E2 (PGE2), which is the product of COX-2 activity. Collectively, our results indicate that E. ictaluri EseN is an important player in the modulation of host immune responses to E.ictaluri infection.

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“…Moreover, IL-6, IL-8, and MCP-1 have been identified as the key factors for induction and are involved in various inflammatory diseases, which are also associated with the severity of inflammatory diseases ( Deshmane et al, 2009 ; Klapproth and Sasaki, 2010 ; Kanmani et al, 2019 ). Previous studies revealed that C. psittaci stimulated various inflammatory factors in monocytes ( He et al, 2015 ). In addition, infection with C. psittaci could also upregulate inflammatory mediators such as IL-6 and IL-8 in different cells containing the cervical epithelioid carcinoma HeLa cell line and the cervical squamous carcinoma SiHa cell line ( He et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies revealed that C. psittaci stimulated various inflammatory factors in monocytes ( He et al, 2015 ). In addition, infection with C. psittaci could also upregulate inflammatory mediators such as IL-6 and IL-8 in different cells containing the cervical epithelioid carcinoma HeLa cell line and the cervical squamous carcinoma SiHa cell line ( He et al, 2015 ). Moreover, in vitro studies have shown that MCP-1 can be produced in the human endothelial cells after chlamydial infection, which is a leading contributor of atherosclerotic lesions characterized by monocyte infiltration ( Molestina et al, 2000 ).…”

Section: Introductionmentioning

confidence: 99%

Chlamydia psittaci Plasmid-Encoded CPSIT_P7 Elicits Inflammatory Response in Human Monocytes via TLR4/Mal/MyD88/NF-κB Signaling Pathway

Chen

Yan

et al. 2020

Front. Microbiol.

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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 κB (NF-κB) signaling pathways in THP-1 cells. Altogether, our results indicate that the CPSIT_P7 induces the TLR4/Mal/MyD88/NF-κB signaling axis and therefore contributes to the inflammatory cytokine response.

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The Type III Secretion System (T3SS) ofChlamydophila psittaciIs Involved in the Host Inflammatory Response by Activating the JNK/ERK Signaling Pathway

Cited by 6 publications

References 40 publications

The Hypothetical Inclusion Membrane Protein CPSIT_0846 Regulates Mitochondrial-Mediated Host Cell Apoptosis via the ERK/JNK Signaling Pathway

The Hypothetical Inclusion Membrane Protein CPSIT_0846 Regulates Mitochondrial-Mediated Host Cell Apoptosis via the ERK/JNK Signaling Pathway

Edwardsiella ictaluri T3SS Effector EseN Modulates Expression of Host Genes Involved in the Immune Response

Chlamydia psittaci Plasmid-Encoded CPSIT_P7 Elicits Inflammatory Response in Human Monocytes via TLR4/Mal/MyD88/NF-κB Signaling Pathway

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