NDLI: CCR1-mediated STAT3 tyrosine phosphorylation and CXCL8 expression in THP-1 macrophage-like cells involve pertussis toxin-insensitive G (14/16) signaling and IL-6 release.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Tam, Issan Y. S. Wong, Yung H. Chui, Ricky K. S. Lee, Maggie M. K. Lau, Alaster H. Y.
Description	Country affiliation: China Author Affiliation: Lee MM ( Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.)
Abstract	Agonists of CCR1 contribute to hypersensitivity reactions and atherosclerotic lesions, possibly via the regulation of the transcription factor STAT3. CCR1 was demonstrated to use pertussis toxin-insensitive G (14/16) to stimulate phospholipase Cß and NF-κB, whereas both G (14) and G (16) are also capable of activating STAT3. The coexpression of CCR1 and G (14/16) in human THP-1 macrophage-like cells suggests that CCR1 may use G (14/16) to induce STAT3 activation. In this study, we demonstrated that a CCR1 agonist, leukotactin-1 (CCL15), could indeed stimulate STAT3 Tyr(705) and Ser(727) phosphorylation via pertussis toxin-insensitive G proteins in PMA-differentiated THP-1 cells, human erythroleukemia cells, and HEK293 cells overexpressing CCR1 and G (14/16). The STAT3 Tyr(705) and Ser(727) phosphorylations were independent of each other and temporally distinct. Subcellular fractionation and confocal microscopy illustrated that Tyr(705)-phosphorylated STAT3 translocated to the nucleus, whereas Ser(727)-phosphorylated STAT3 was retained in the cytosol after CCR1/G (14) activation. CCL15 was capable of inducing IL-6 and IL-8 (CXCL8) production in both THP-1 macrophage-like cells and HEK293 cells overexpressing CCR1 and G (14/16). Neutralizing Ab to IL-6 inhibited CCL15-mediated STAT3 Tyr(705) phosphorylation, whereas inhibition of STAT3 activity abolished CCL15-activated CXCL8 release. The ability of CCR1 to signal through G (14/16) provides a linkage for CCL15 to regulate IL-6/STAT3-signaling cascades, leading to expression of CXCL8, a cytokine that is involved in inflammation and the rupture of atherosclerotic plaque.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	11
Volume Number	189
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-12-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Gtp-binding Protein Alpha Subunits, Gq-g11 Immunology Interleukin-6 Interleukin-8 Macrophages Receptors, Ccr1 Stat3 Transcription Factor Antibodies Pharmacology Cell Nucleus Drug Effects Genetics Chemokines, Cc Cytosol Gene Expression Hek293 Cells Antagonists & Inhibitors Biosynthesis K562 Cells Macrophage Inflammatory Proteins Cytology Pertussis Toxin Phosphorylation Plasmids Protein Isoforms Agonists Serine Metabolism Signal Transduction Transfection Tyrosine Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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