scholarly journals Antiapoptotic activity of Chlamydia trachomatis Pgp3 protein involves activation of the ERK1/2 pathway mediated by upregulation of DJ-1 protein

2019 ◽  
Vol 77 (9) ◽  
Author(s):  
Fangzhen Luo ◽  
Mingyi Shu ◽  
Silu Gong ◽  
Yating Wen ◽  
Bei He ◽  
...  
Keyword(s):  
Chlamydia Trachomatis ◽  
Hela Cells ◽  
Signal Pathway ◽  
Immune Defense ◽  
Apoptosis Resistance ◽  
Host Cell Apoptosis ◽  
Pathway Activation ◽  
Tnf Α ◽  
Antiapoptotic Activity

ABSTRACT Chlamydia trachomatis has evolved strategies to prevent host cell apoptosis to evade the host immune defense. However, the precise mechanisms of antiapoptotic activity of C. trachomatis still need to be clarified. Pgp3, one of eight plasmid proteins of C. trachomatis, has been identified to be closely associated with chlamydial virulence. In this study, we attempted to explore the effects and the mechanisms of Pgp3 protein on apoptosis in HeLa cells; the results showed that Pgp3 increased Bcl-2/Bax ratio and prevented caspase-3 activation to suppress apoptosis induced by TNF-α and cycloheximide (CHX) through ERK1/2 pathway activation. Downregulation of DJ-1 with siRNA-DJ-1(si-DJ-1) reduced ERK1/2 phosphorylation and elevated apoptotic rate significantly in Pgp3-HeLa cells. However, inhibition of ERK1/2 signal pathway with ERK inhibitor PD98059 had little effect on DJ-1 expression. These findings confirm that plasmid protein Pgp3 contributes to apoptosis resistance through ERK1/2 signal pathway mediated by upregulation of DJ-1 expression. Therefore, the present study provided novel insights into the role of Pgp3 in apoptosis and suggested that manipulation of the host apoptosis response could be a new approach for the prevention and treatment of C. trachomatis infection.

Role of Exercise Activity in Alleviating Neuropathic Pain in Diabetes via Inhibition of the Pro-Inflammatory Signal Pathway

2018 ◽  
Vol 21 (1) ◽  
pp. 14-21 ◽  
Author(s):  
Xiao-Qiu Ma ◽  
Jing Qin ◽  
Hong-Yan Li ◽  
Xiu-Li Yan ◽  
Yong Zhao ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Tumor Necrosis ◽  
Signal Pathway ◽  
Sensory Nerves ◽  
Glucose Levels ◽  
Tnf Α ◽  
Exercise Activity ◽  
Necrosis Factor ◽  
Pro Inflammatory Cytokines

Hyperalgesia and allodynia are commonly observed in patients with diabetic neuropathy. The treatment and management of painful peripheral neuropathy is important in these patients. The purpose of this study was to examine the role of exercise in modulating neuropathic pain induced by diabetes. Diabetes was induced in rats by an intraperitoneal injection of streptozotocin (STZ). Control rats received saline injections. Groups included control rats without exercise (NT-control, n = 12), control rats with exercise (EX-control, n = 16), STZ rats without exercise (NT-STZ, n = 18), and STZ rats with exercise (EX-STZ, n = 22). Rats in EX groups ran on a treadmill 4 days/week for 5 weeks beginning from the week of STZ administration. Mechanical hypersensitivity (mechanical paw withdrawal thresholds [PWTs]) and glucose levels were tested weekly. Then, enzyme-linked immunoassay and Western blot analysis were used to determine the levels of pro-inflammatory cytokines (PICs) and their receptors in sensory nerves. PWTs were significantly increased after 4–5 weeks of exercise in STZ rats ( p < .05 vs. NT-STZ rats). Inhibition of neuropathic pain by exercise in STZ rats was accompanied by decreases in interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α levels and downregulated expression of their receptors. Furthermore, blocking individual PIC receptors elevated PWTs to a greater degree in STZ rats ( p < .05 vs. control rats). Overall, our data suggest that exercise can play a role in improving neuropathic pain induced by STZ and that PIC signaling is a part of the mechanism involved in this effect.

scholarly journals Persistent Chlamydia trachomatis Infection of HeLa Cells Mediates Apoptosis Resistance through a Chlamydia Protease-Like Activity Factor-Independent Mechanism and Induces High Mobility Group Box 1 Release

2011 ◽  
Vol 80 (1) ◽  
pp. 195-205 ◽  
Author(s):  
Jürgen Rödel ◽  
Christina Große ◽  
Hangxing Yu ◽  
Katharina Wolf ◽  
Gordon P. Otto ◽  
...  
Keyword(s):  
Chlamydia Trachomatis ◽  
Host Cell ◽  
Hela Cells ◽  
Persistent Infection ◽  
High Mobility ◽  
Apoptosis Resistance ◽  
Content Type ◽  
Activity Factor ◽  
Infected Cells ◽  
Ifn Γ

ABSTRACTIntracellular persistence ofChlamydia trachomatishas been implicated in the development of chronic infection that can result in pelvic inflammatory disease and tubal sterility. By inhibition of host cell apoptosis, chlamydiae have evolved a strategy to maintain the intracellular environment for replication and persistence. Both antiapoptotic host cell-derived factors and the chlamydial protease-like activity factor (CPAF) are involved inChlamydia-mediated apoptosis resistance. Here, we show that in HeLa cells infected with gamma interferon (IFN-γ)-induced persistentC. trachomatisserovar D, the expression of CPAF is downregulated, and proapoptotic protease substrates are not cleaved. Persistent infection protected HeLa cells from apoptosis when they were exposed to staurosporine. Small-interfering RNA-mediated inhibition of myeloid cell leukemia 1 (Mcl-1) protein upregulation sensitized persistently infected cells for apoptosis. The inhibitor of apoptosis protein 2 (IAP-2) seems not to be relevant in this context because IAP-2 protein was not induced in response to IFN-γ treatment. Although apoptosis was inhibited, persistent infection caused cell membrane disintegration, as measured by the increased release of cytokeratin 18 from HeLa cells. Moreover, persistently infected cells released significantly increased amounts of high mobility group box 1 (HMGB1) protein which represents a proinflammatory damage-associated pattern molecule. The data of this study suggest that cells infected with persistentC. trachomatisare protected from apoptosis independently of CPAF but may promote chronic inflammation through HMGB1 release.

scholarly journals Remimazolam Protects Against LPS-Induced Endotoxicity Improving Survival of Endotoxemia Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaolei Liu ◽  
Shaoping Lin ◽  
Yiyue Zhong ◽  
Jiaojiao Shen ◽  
Xuedi Zhang ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Signal Pathway ◽  
Tlr4 Expression ◽  
Tnf Α ◽  
Sedative Drugs ◽  
Mapk Signal Pathway ◽  
Lps Treatment

Remimazolam is a new benzodiazepine of sedative drugs with an ultra-short-acting anesthetic effect, commonly used for critically ill patients (especially septic patients) in intensive care units (ICUs). Although some anesthetics have been reported to show certain anti-inflammatory effects, the role of remimazolam in inflammation is still remained unknown. Here, we studied the effects of remimazolam on macrophage in response to LPS both in vivo and in vitro. Interestingly, compared with LPS treatment group, remimazolam remarkably improved survival rate of endotoxemia mice and decreased the release of LPS-induced inflammatory mediators (such as TNF-α, IL-6, and IL-1β). We further found that remimazolam not only inhibited the activation of MAPK signal pathway at 15 min after LPS treatment but also disturbed Rab5a related TLR4 expression at cell surface in response to LPS at a later time. Such evidence suggests that remimazolam might be beneficial to septic patients who are suffering from uncontrolled inflammatory responses.

scholarly journals Differences in Innate Immune Responses (In Vitro) to HeLa Cells Infected with Nondisseminating Serovar E and Disseminating Serovar L2 of Chlamydia trachomatis

2002 ◽  
Vol 70 (6) ◽  
pp. 3234-3248 ◽  
Author(s):  
Sophie Dessus-Babus ◽  
Toni L. Darville ◽  
Francis P. Cuozzo ◽  
Kaethe Ferguson ◽  
Priscilla B. Wyrick
Keyword(s):  
Chlamydia Trachomatis ◽  
Inflammatory Response ◽  
Proinflammatory Cytokines ◽  
Hela Cells ◽  
Mrna Level ◽  
Necrosis Factor Alpha ◽  
Apical Side ◽  
Tnf Α ◽  
Infected Cells

ABSTRACT The inflammatory response associated with Chlamydia trachomatis genital infections is thought to be initiated by the release of proinflammatory cytokines from infected epithelial cells. This study focuses on the interactions between C. trachomatis-infected HeLa cells and immune cells involved in the early stages of infection, i.e., neutrophils and macrophages. First, we showed that the expression of interleukin-11 (IL-11), an anti-inflammatory cytokine mainly active on macrophages, was upregulated at the mRNA level in the genital tracts of infected mice. Second, incubation of differentiated THP-1 (dTHP-1) cells or monocyte-derived macrophages (MdM) with basal culture supernatants from C. trachomatis serovar E- or serovar L2-infected HeLa cells resulted in macrophage activation with a differential release of tumor necrosis factor alpha (TNF-α) and upregulation of indoleamine 2,3-deoxygenase (IDO) but not of Toll-like receptor 2 and 4 mRNA expression. Third, coculture of infected HeLa cells with dTHP-1 cells resulted in a reduction in chlamydial growth, which was more dramatic for serovar E than for L2 and which was partially reversed by the addition of anti-TNF-α antibodies for serovar E or exogenous tryptophan for both serovars but was not reversed by the addition of superoxide dismutase or anti-IL-8 or anti-IL-1β antibodies. A gamma interferon-independent IDO mRNA upregulation was also detected in dTHP-1 cells from infected cocultures. Lastly, with a two-stage coculture system, we found that (i) supernatants from neutrophils added to the apical side of infected HeLa cell cultures were chlamydicidal and induced MdM to express antichlamydial activity and (ii) although polymorphonuclear leukocytes released more proinflammatory cytokines in response to serovar E- than in response to L2-infected cells, MdM were strongly activated by serovar L2 infection, indicating that the early inflammatory response generated with a nondisseminating or a disseminating strain is different.

scholarly journals Role of Viral Factor E3L in Modified Vaccinia Virus Ankara Infection of Human HeLa Cells: Regulation of the Virus Life Cycle and Identification of Differentially Expressed Host Genes

2005 ◽  
Vol 79 (4) ◽  
pp. 2584-2596 ◽  
Author(s):  
Holger Ludwig ◽  
Jörg Mages ◽  
Caroline Staib ◽  
Michael H. Lehmann ◽  
Roland Lang ◽  
...  
Keyword(s):  
Life Cycle ◽  
Vaccinia Virus ◽  
Hela Cells ◽  
Immune Defense ◽  
Oligoadenylate Synthetase ◽  
Molecular Monitoring ◽  
Late Gene Expression ◽  
Modified Vaccinia Virus Ankara ◽  
Inducible Protein

ABSTRACT Modified vaccinia virus Ankara (MVA) is a highly attenuated virus strain being developed as a vaccine for delivery of viral and recombinant antigens. The MVA genome lacks functional copies of numerous genes interfering with host response to infection. The interferon resistance gene E3L encodes one important viral immune defense factor still made by MVA. Here we demonstrate an essential role of E3L to allow for completion of the MVA molecular life cycle upon infection of human HeLa cells. A deletion mutant virus, MVA-ΔE3L, was found defective in late protein synthesis, viral late transcription, and viral DNA replication in infected HeLa cells. Moreover, we detected viral early and continuing intermediate transcription associated with degradation of rRNA, indicating rapid activation of 2′-5′-oligoadenylate synthetase/RNase L in the absence of E3L. Further molecular monitoring of E3L function by microarray analysis of host cell transcription in MVA- or MVA-ΔE3L-infected HeLa cells revealed an overall significant down regulation of more than 50% of cellular transcripts expressed under mock conditions already at 5 h after infection, with a more prominent shutoff following MVA-ΔE3L infection. Interestingly, a cluster of genes up regulated exclusively in MVA-ΔE3L-infected cells could be identified, including transcripts for interleukin 6, growth arrest and DNA damage-inducible protein β, and dual-specificity protein phosphatases. Our data indicate that lack of E3L inhibits MVA antigen production in human HeLa cells at the level of viral late gene expression and suggest that E3L can prevent activation of additional host factors possibly affecting the MVA molecular life cycle.

scholarly journals Lactobacillus crispatus BC1 Biosurfactant Counteracts the Infectivity of Chlamydia trachomatis Elementary Bodies

2021 ◽  
Vol 9 (5) ◽  
pp. 975
Author(s):  
Claudio Foschi ◽  
Carola Parolin ◽  
Barbara Giordani ◽  
Sara Morselli ◽  
Barbara Luppi ◽  
...  
Keyword(s):  
Chlamydia Trachomatis ◽  
Hela Cells ◽  
Myristic Acid ◽  
Contact Time ◽  
Therapeutic Agents ◽  
Inhibitory Effects ◽  
Sexually Transmitted ◽  
Lactobacillus Crispatus ◽  
Novel Therapeutic

Lactobacilli-derived biosurfactants (BS) have shown promising effects as antimicrobial molecules. Since Lactobacillus crispatus plays a crucial role in maintaining vaginal eubiosis, BS from this species could represent novel therapeutic agents to counteract sexually transmitted pathogens, such as Chlamydia trachomatis (CT). The aim of the present study was to assess the inhibitory effects of a BS produced by the vaginal strain L. crispatus BC1 on the infectivity of CT elementary bodies (EBs). For concentrations ranging between 1 and 0.5 mg/mL at 60-min contact time, L. crispatus BC1 BS displayed a highly significant anti-CT activity, with about 50% reduction of EB infectivity towards HeLa cells. To identify the components responsible for chlamydial inhibition, a panel of selected fatty acids, including those present in BS lipopeptidic structure, was tested against CT EBs. Pentadecanoic acid, myristic acid, β-hydroxy-myristic acid, and β-hydroxy-palmitic acid were able to significantly reduce EBs infectivity up to 5–0.5 µg/mL, concentrations that resulted to be non-toxic for HeLa cells. These data can contribute to the understanding of the biological role of lactobacilli in the vaginal niche, as well as to promote the application of their produced BS as an innovative and antibiotic-sparing anti-chlamydial strategy.

scholarly journals Role of the Parasite-Derived Prostaglandin D2 in the Inhibition of Epidermal Langerhans Cell Migration during Schistosomiasis Infection

2001 ◽  
Vol 193 (10) ◽  
pp. 1135-1148 ◽  
Author(s):  
Véronique Angeli ◽  
Christelle Faveeuw ◽  
Olivier Roye ◽  
Josette Fontaine ◽  
Elisabeth Teissier ◽  
...  
Keyword(s):  
Defense Mechanisms ◽  
Interleukin 10 ◽  
Inhibitory Effect ◽  
Immune Defense ◽  
Contact Hypersensitivity ◽  
Prostaglandin D2 ◽  
Host Immune System ◽  
Tnf Α ◽  
Contact Allergen

Epidermal Langerhans cells (LCs) play a key role in immune defense mechanisms and in numerous immunological disorders. In this report, we show that percutaneous infection of C57BL/6 mice with the helminth parasite Schistosoma mansoni leads to the activation of LCs but, surprisingly, to their retention in the epidermis. Moreover, using an experimental model of LC migration induced by tumor necrosis factor (TNF)-α, we show that parasites transiently impair the departure of LCs from the epidermis and their subsequent accumulation as dendritic cells in the draining lymph nodes. The inhibitory effect is mediated by soluble lipophilic factors released by the parasites and not by host-derived antiinflammatory cytokines, such as interleukin-10. We find that prostaglandin (PG)D2, but not the other major eicosanoids produced by the parasites, specifically impedes the TNF-α–triggered migration of LCs through the adenylate cyclase–coupled PGD2 receptor (DP receptor). Moreover, the potent DP receptor antagonist BW A868C restores LC migration in infected mice. Finally, in a model of contact allergen-induced LC migration, we show that activation of the DP receptor not only inhibits LC emigration but also dramatically reduces the contact hypersensitivity responses after challenge. Taken together, we propose that the inhibition of LC migration could represent an additional stratagem for the schistosomes to escape the host immune system and that PGD2 may play a key role in the control of cutaneous immune responses.

The potential protective role of the combination of IL-22 and TNF-α against genital tract Chlamydia trachomatis infection

Cytokine ◽  
2015 ◽  
Vol 73 (1) ◽  
pp. 66-73 ◽  
Author(s):  
Xiumin Zhao ◽  
Danyang Zhu ◽  
Jiangbin Ye ◽  
Xingqun Li ◽  
Zhibin Wang ◽  
...  
Keyword(s):  
Chlamydia Trachomatis ◽  
Genital Tract ◽  
Protective Role ◽  
Chlamydia Trachomatis Infection ◽  
Tnf Α

scholarly journals Chlamydia trachomatis Induces Remodeling of the Actin Cytoskeleton during Attachment and Entry into HeLa Cells

2002 ◽  
Vol 70 (7) ◽  
pp. 3793-3803 ◽  
Author(s):  
Reynaldo A. Carabeo ◽  
Scott S. Grieshaber ◽  
Elizabeth Fischer ◽  
Ted Hackstadt
Keyword(s):  
Chlamydia Trachomatis ◽  
Cell Surface ◽  
Actin Cytoskeleton ◽  
Hela Cells ◽  
Actin Polymerization ◽  
Cytochalasin D ◽  
Actin Remodeling ◽  
Ultrastructural Studies ◽  
Infected Cells

ABSTRACT To elucidate the host cell machinery utilized by Chlamydia trachomatis to invade epithelial cells, we examined the role of the actin cytoskeleton in the internalization of chlamydial elementary bodies (EBs). Treatment of HeLa cells with cytochalasin D markedly inhibited the internalization of C. trachomatis serovar L2 and D EBs. Association of EBs with HeLa cells induced localized actin polymerization at the site of attachment, as visualized by either phalloidin staining of fixed cells or the active recruitment of GFP-actin in viable infected cells. The recruitment of actin to the specific site of attachment was accompanied by dramatic changes in the morphology of cell surface microvilli. Ultrastructural studies revealed a transient microvillar hypertrophy that was dependent upon C. trachomatis attachment, mediated by structural components on the EBs, and cytochalasin D sensitive. In addition, a mutant CHO cell line that does not support entry of C. trachomatis serovar L2 did not display such microvillar hypertrophy following exposure to L2 EBs, which is in contrast to infection with serovar D, to which it is susceptible. We propose that C. trachomatis entry is facilitated by an active actin remodeling process that is induced by the attachment of this pathogen, resulting in distinct microvillar reorganization throughout the cell surface and the formation of a pedestal-like structure at the immediate site of attachment and entry.

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