title: Suppressor of cytokine signaling 3 inhibits head kidney macrophage activation and cytokine expression in Scophthalmus maximus.
abstract: Proteins of the suppressor of cytokine signaling (SOCS) family function as inducible feedback inhibitors of cytokine signaling via the JAK/STAT pathway. Although several SOCS isoforms have been identified in teleosts, their immunological functions remain largely unknown. In this study, we identified in turbot Scophthalmus maximus a SOCS homologue (named SmSOCS3) of the mammalian SOCS3 type. The deduced amino acid sequence of SmSOCS3 contains 205 residues and shares extensive overall identities (60-82%) with those of known fish SOCS3. In silico analyses revealed that, like typical SOCS3, SmSOCS3 possesses a kinase inhibitor region (KIR), a Src homology 2 (SH2) domain, and a SOCS box domain. Under physiological conditions SmSOCS3 expression was detected, in increasing order, in blood, brain, heart, kidney, liver, spleen, muscle, and gill. Experimental infection of turbot with a bacterial pathogen induced significant SmSOCS3 expression in kidney, spleen, liver, and gill in time-dependent manners. Examination of SmSOCS3 expression in head kidney (HK) macrophages showed that SmSOCS3 transcription was significantly upregulated in the presence of purified recombinant TNF-α. On the other hand, SmSOCS3 overexpression in HK macrophages inhibited the transcription of TNF-α as well as IL-1β and CC-chemokine. In addition, SmSOCS3 overexpression significantly reduced macrophage respiratory burst activity, nitric oxide production, and bactericidal activity. Taken together, these results suggest that SmSOCS3 is a cytokine-inducible suppressor of pro-inflammatory cytokine signaling in HK macrophages and that regulated expression of SmSOCS3 is required for optimal innate immune response against bacterial infection.
authors.affiliation: Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, 7 Nanhai Road, Qingdao 266071, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Zhi-zhong
authors.initials: ZZ
authors.lastname: Xiao
authors.forename: Li
authors.initials: L
authors.lastname: Sun
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005393:Fish Diseases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005412:Flatfishes / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015870:Gene Expression; D016905:Gram-Negative Bacterial Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000662:veterinary*; D007113:Immunity, Innate; D007249:Inflammation; D053583:Interleukin-1beta / Q000235:genetics; D053526:Listonella / Q000276:immunology; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008969:Molecular Sequence Data; D012097:Repressor Proteins / Q000235:genetics; D016897:Respiratory Burst; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D012097:Repressor Proteins; D050826:Suppressor of Cytokine Signaling Proteins; D014409:Tumor Necrosis Factor-alpha