title: Soluble interleukin-6 receptor is elevated during influenza A virus infection and mediates the IL-6 and IL-32 inflammatory cytokine burst.
abstract: Influenza A virus (IAV) infection is a major worldwide public health problem. However, the factors involved in mediating the inflammatory response to this infection and their relationships remain poorly understood. Here, we show that IAV infection stimulates the expression of the soluble IL-6 receptor (sIL-6R), a multifunctional protein involved in IL-6 signaling. Interestingly, sIL-6R expression upregulated the levels of its own ligand, IL-6 and those of the pro-inflammatory cytokine IL-32. shRNA-mediated knockdown of sIL-6R suppressed IL-6 and IL-32, indicating that this regulation is dependent on sIL-6R during IAV infection. Furthermore, our results demonstrate that IL-32 participates in a negative feedback loop that inhibits sIL-6R while upregulating IL-6 expression during IAV infection. Therefore, we show that sIL-6R is a critical cellular factor involved in the acute inflammatory response to viral infection.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Han
authors.forename: Yong-Kui
authors.initials: YK
authors.lastname: Li
authors.forename: Sheng-Li
authors.initials: SL
authors.lastname: Zhu
authors.forename: Fang
authors.initials: F
authors.lastname: Ao
authors.forename: Jian
authors.initials: J
authors.lastname: Feng
authors.forename: Ming-Zhen
authors.initials: MZ
authors.lastname: Jing
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Lin-Bai
authors.initials: LB
authors.lastname: Ye
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D000328:Adult; D003710:Demography; D025461:Feedback, Physiological; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D009980:Influenza A virus / Q000276:immunology / Q000502:physiology*; D007251:Influenza, Human / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D015850:Interleukin-6 / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism*; D008297:Male; D018448:Models, Immunological; D011401:Promoter Regions, Genetic / Q000235:genetics; D019947:Receptors, Interleukin-6 / Q000378:metabolism*; D012995:Solubility; D015854:Up-Regulation
chemical_list: C496971:IL32 protein, human; D015850:Interleukin-6; D007378:Interleukins; D019947:Receptors, Interleukin-6