title: Azithromycin treatment modulates the extracellular signal-regulated kinase mediated pathway and inhibits inflammatory cytokines and chemokines in epithelial cells from infertile women with recurrent Chlamydia trachomatis infection.
abstract: Epidemiological and animal model studies suggest that sequelae of genital Chlamydia trachomatis infection are more often associated with second or subsequent infections than with initial infection. Further, in order to establish an acute or long-term persistent infection, C. trachomatis develops several strategies to circumvent host immune responses. Hence, resolution of the C. trachomatis infection may require modulation of host factors especially during persistent or chronic infection. Moreover, azithromycin treatment has been reported to possess anti-inflammatory properties but its mechanism of action is still not elucidated. Therefore, in order to better understand the effect of azithromycin in chronic conditions, our aim was to study changes in expression of key genes associated with inflammatory cytokines and receptors, mitogen-activated protein kinase (MAPK) signaling pathway, and apoptosis pathway before and after therapy with azithromycin in infertile women with recurrent C. trachomatis infection. Real-time polymerase chain reaction was performed to study inflammatory cytokines and receptors, MAPK signaling pathway, and apoptosis pathway before and after therapy with azithromycin in infertile women with recurrent C. trachomatis infection. Further, effect of azithromycin on activation of extracellular signal-regulated kinase was studied in epithelial cells by western blotting. Chemokine (C-C motif) ligand 2 (CCL2), CCL5, chemokine (C-X-C motif) ligand 1 (CXCL1), CXCL5, CXCL9, interleukin-1B (IL-1B), IL-8, baculoviral IAP repeat-containing 3 (BIRC3), myeloid cell leukemia sequence 1 (MCL1), and MAPK1 were downregualted after azithromycin treatment. In addition, phosphorylation of extracellular signal-regulated kinase was inhibited after azithromycin treatment in epithelial cells obtained from women with recurrent infection. Hence, our data suggest that azithromycin with its properties apart from antibacterial activity may contribute to its therapeutic potential in treatment of chronic recurrent infection in infertile women.
authors: Institute of Pathology, Indian Council of Medical Research, New Delhi, India.
authors: Pragya
authors: P
authors: Srivastava
authors: Harsh
authors: H
authors: Vardhan
authors: Apurb Rashmi
authors: AR
authors: Bhengraj
authors: Rajneesh
authors: R
authors: Jha
authors: Laishram Chandreshwor
authors: LC
authors: Singh
authors: Sudha
authors: S
authors: Salhan
authors: Aruna
authors: A
authors: Mittal
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D017963:Azithromycin / Q000494:pharmacology*; D018925:Chemokines / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D002690:Chlamydia Infections / Q000150:complications*; D002692:Chlamydia trachomatis / Q000472:pathogenicity; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007247:Infertility, Female / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D007249:Inflammation / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000900:Anti-Bacterial Agents; D018925:Chemokines; D018121:Receptors, Cytokine; D017963:Azithromycin; D048049:Extracellular Signal-Regulated MAP Kinases