title: Interleukin-4 and interleukin-13 inhibit the expression of leukemia inhibitory factor and interleukin-11 in fibroblasts.
abstract: Cytokines produced by inflammatory or resident mesenchymal cells play important modulatory roles in the pathogenesis of inflammation induced bone loss. In the present study, the effects of IL-4 and IL-13 on the expression of three osteotropic cytokines in the IL-6 family expressed in human gingival fibroblasts were studied. IL-4Rα and IL-13Rα1 mRNA were constitutively expressed in human gingival fibroblasts. The inflammatory cytokines IL-1β and TNF-α increased expression of IL-6, LIF, and IL-11 mRNA and protein in the gingival fibroblasts. Addition of IL-4 or IL-13 had no effect on IL-6 expression, but significantly inhibited LIF and IL-11 mRNA and protein stimulated by IL-1β and TNF-α. No involvement of NF-κB or STAT1 was observed in the inhibition. STAT6 was phosphorylated at Y641 by treatment with IL-4 and knockdown of STAT6 with siRNA decreased the inhibition of IL-11 and LIF expression by IL-4 in IL-1β and TNF-α stimulated cells. This study suggests that activation of STAT6 by IL-4 and IL-13, through type 2 IL-4 receptors, inhibits production of IL-11 and LIF stimulated by IL-1β and TNF-α in human gingival fibroblasts. A negative modulatory role of IL-4 and IL-13 in osteotropic cytokine production could be a mechanism playing an important inhibitory role in inflammation induced periodontitis.
authors.affiliation: Department of Molecular Periodontology, Umeå University, Umeå, Sweden.
authors.forename: Pedro P C
authors.initials: PP
authors.lastname: Souza
authors.forename: Py
authors.initials: P
authors.lastname: Palmqvist
authors.forename: Pernilla
authors.initials: P
authors.lastname: Lundberg
authors.forename: Inger
authors.initials: I
authors.lastname: Lundgren
authors.forename: Lennart
authors.initials: L
authors.lastname: Hänström
authors.forename: João A C
authors.initials: JA
authors.lastname: Souza
authors.forename: H Herschel
authors.initials: HH
authors.lastname: Conaway
authors.forename: Ulf H
authors.initials: UH
authors.lastname: Lerner
mesh_terms: D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism*; D005881:Gingiva / Q000378:metabolism; D006801:Humans; D017370:Interleukin-11 / Q000235:genetics / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism*; D053605:Leukemia Inhibitory Factor / Q000235:genetics* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D053660:Receptors, Interleukin-13 / Q000235:genetics / Q000378:metabolism; D019948:Receptors, Interleukin-4 / Q000235:genetics / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000378:metabolism
chemical_list: C508611:IL11 protein, human; C508598:IL4 protein, human; D017370:Interleukin-11; D018793:Interleukin-13; D007378:Interleukins; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D016328:NF-kappa B; D012333:RNA, Messenger; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015847:Interleukin-4