title: Ferritin heavy chain-mediated iron homoeostasis regulates expression of IL-10 in Chlamydia trachomatis-infected HeLa cells.
abstract: Chlamydia trachomatis is the leading cause of sexually transmitted infection worldwide, in which disease outcome is determined by the balance between pro- and anti-inflammatory host immune responses. Iron plays important roles in regulation and enhancement of various pro- and anti-inflammatory cytokines. Earlier studies have established essentiality of iron in C. trachomatis infection; however, there is lack of study wherein modulatory effect of iron regulated protein [FHC (ferritin heavy chain)] in regulation of anti-inflammatory cytokine IL (interleukin)-10 has been investigated. In this study, immunoblotting results showed the up-regulation of FHC in C. trachomatis-infected HeLa cells in comparison with mock (in vitro control). Further secretory IL-10 level was significantly increased (P<0.001) or decreased (P<0.001) in response to iron supplementation [FAC (ferric ammonium citrate)] and depletion [DFO (deferoxamine)], respectively. However, in C. trachomatis-infected HeLa cells, levels of IL-10 remain higher, irrespective of availability of iron in comparison with their respective control. These results showed that secretion of IL-10 and expressions of FHC have concordance. Further, to understand interdependence of IL-10 and iron homoeostasis (regulation), the levels of IL-10 were compared with iron-responsive GFP (green fluorescent protein) expression in HeLa-229 cells. The mean fluorescent intensities of GFP were in accordance with levels of IL-10 in C. trachomatis-infected cells. These results showed the association of secreted IL-10, FHC and iron homoeostasis in C. trachomatis-infected HeLa-229 cells. This study provides insight into host-Chlamydia interaction at the crossroad of iron metabolism and immune responses and may help in realizing the potential of iron homoeostasis modulators in treatment of chronic chlamydial infection.
authors.affiliation: Institute of Pathology, Indian Council of Medical Research ICMR, Safdarjung Hospital Campus, Post Box No. 4909, New Delhi110029, India.
authors.forename: Harsh
authors.initials: H
authors.lastname: Vardhan
authors.forename: Rishein
authors.initials: R
authors.lastname: Gupta
authors.forename: Rajneesh
authors.initials: R
authors.lastname: Jha
authors.forename: Apurb Rashmi
authors.initials: AR
authors.lastname: Bhengraj
authors.forename: Aruna
authors.initials: A
authors.lastname: Mittal
mesh_terms: D001052:Apoferritins / Q000235:genetics / Q000378:metabolism*; D002692:Chlamydia trachomatis; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology; D005290:Ferric Compounds / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D006367:HeLa Cells; D006706:Homeostasis; D006801:Humans; D015151:Immunoblotting; D016753:Interleukin-10 / Q000096:biosynthesis*; D007501:Iron / Q000378:metabolism* / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology
chemical_list: D016207:Cytokines; D005290:Ferric Compounds; C508609:IL10 protein, human; D000644:Quaternary Ammonium Compounds; D016753:Interleukin-10; D049452:Green Fluorescent Proteins; D001052:Apoferritins; D007501:Iron; D003676:Deferoxamine; C013531:ferric ammonium citrate