title: Effect of IFN-α on KC and LIX expression: role of STAT1 and its effect on neutrophil recruitment to the spleen after lipopolysaccharide stimulation.
abstract: The spleen is a crucial lymphoid organ. It is involved in the recruitment of various immunocytes to their correct locations using specific chemokines, but little is known concerning the role of type-I interferon (IFN) in the regulation of chemokines. In this study, we first used protein microarrays to assess the expression of keratinocyte-derived chemokine (KC) and lipopolysaccharide-induced CXC chemokine (LIX) in murine spleens. Both expressions were smoothly enhanced by IFN-α pretreatment after LPS injection. Then, we focused on the IFN-α regulation of KC, LIX, and their target cells, neutrophils, using an IFN-α neutralizing antibody and fludarabine (specific signal transducers and activators of transcription 1 - STAT1 inhibitor). Next, LPS was found to attenuate the production of KC and LIX in spleen. Even the elevated production of chemokines caused by exogenous IFN-α was found to be attenuated by fludarabine pretreatment. We later determined that the marginal zone and red pulp are the main sites of KC and LIX production. Last, we determined that the number of neutrophils was slightly increased by IFN-α treatment and diminished by IFN-α neutralization or fludarabine treatment. Further, the elevated neutrophils due to exogenous IFN-α were partially reversed by fludarabine pretreatment. In this way, these results indicate that IFN-α facilitates KC and LIX expression in mouse spleens after an LPS challenge. This effect was found to be mainly dependent upon the activation of STAT1, it may be involved in the recruitment of neutrophils to the spleen for the clearance of pathogens.
authors: Key Laboratory of Hepatosplenic Surgery, Department of General Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors: Huayang
authors: H
authors: Pan
authors: Yong
authors: Y
authors: Ma
authors: Dawei
authors: D
authors: Wang
authors: Jizhou
authors: J
authors: Wang
authors: Hongchi
authors: H
authors: Jiang
authors: Shangha
authors: S
authors: Pan
authors: Baolei
authors: B
authors: Zhao
authors: Yaohua
authors: Y
authors: Wu
authors: Dongsheng
authors: D
authors: Xu
authors: Xueying
authors: X
authors: Sun
authors: Lianxin
authors: L
authors: Liu
authors: Zhilin
authors: Z
authors: Xu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018925:Chemokines / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019743:Chemokines, CXC / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D007093:Imidazoles / Q000276:immunology / Q000494:pharmacology; D007150:Immunohistochemistry; D016898:Interferon-alpha / Q000276:immunology* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D011725:Pyridines / Q000276:immunology / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D014740:Vidarabine / Q000031:analogs & derivatives / Q000276:immunology / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism
chemical_list: D018925:Chemokines; D019743:Chemokines, CXC; D007093:Imidazoles; D016898:Interferon-alpha; D008070:Lipopolysaccharides; D011725:Pyridines; D050794:STAT1 Transcription Factor; C074302:keratinocyte-derived chemokines; D048051:p38 Mitogen-Activated Protein Kinases; D014740:Vidarabine; C093642:SB 203580; C024352:fludarabine