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Protein tyrosine kinase and mitogen-activated protein kinase signaling pathways contribute to differences in heterophil-mediated innate immune responsiveness between two lines of broilers

Swaggerty, C. L., He, H., Genovese, K. J., Pevzner, I. Y., Kogut, M. H.
Avian pathology 2011 v.40 no.3 pp. 289
Salmonella enteritidis, broiler chickens, chemokines, gene expression regulation, heterophils, immunity, mitogen-activated protein kinase, mitogen-activated protein kinase kinase, mitogen-activated protein kinase kinase kinase, protein phosphorylation, protein-tyrosine kinases, salmonellosis, signal transduction, transcription factor NF-kappa B, tyrosine
Protein tyrosine phosphorylation mediates signal transduction of cellular processes with protein tyrosine kinases (PTKs) regulating virtually all signalling events. The mitogen-activated protein kinase (MAPK) super-family consists of three conserved pathways that convert receptor activation into cellular functions:extracellular response kinases (ERK), c-Jun N-terminal kinases (JNK) and p38. Previously conducted studies using two chicken lines (A and B) show line A heterophils are functionally more responsive and produce a differential cytokine/chemokine profile compared with line B, which also translates to increased resistance to bacterial challenges. Therefore, we hypothesize the differences between the lines result from distinctive signalling cascades that mediate heterophil function. Heterophils from lines A and B were isolated from 1-day-old chickens and total phosphorylated PTK and p38, JNK, ERK, and transcription factor (activator protein 1 (AP-1) and nuclear factor kappa B (NF-kB)) protein levels quantified following interaction with Salmonella Enteritidis (SE). Control and SE-treated heterophils from line A had greater (P50.05) PTK phosphorylation compared to line B with increased (P50.05) activation of p38. Conversely, line B heterophils activated JNK (P50.05). There were no differences in ERK between control and activated heterophils for either line. Defined signalling inhibitors were used to show specificity. The AP-1 and NF-kB transcription factor families were also examined, and c-Jun and p50, respectively, were the only members different between the lines and both were up-regulated in line A compared with line B. These data indicate that increased responsiveness of line A heterophils is mediated, largely, by an increased ability to activate PTKs, the p38 MAPK pathway and specific transcription factors, all of which directly affect the innate immune response.