ARS | Publication request: Up-Regulation of Nitric Oxide Synthesis by Tlr9 Agonist Cpg Oligodeoxynucleotide in Chicken Monocytes Via Activation of Erk, P38 Mapk, Jnk, and Nf-Kappab Signal Pathways

Submitted to: Avian Immunology Research Group Abstract
Publication Type: Abstract
Publication Acceptance Date: June 1, 2004
Publication Date: September 4, 2004
Citation: He, H., Kogut, M.H. 2004. Up-regulation of nitric oxide synthesis by TLR9 agonist CpG oligodeoxynucleotide in chicken monocytes via activation of ERK, p38 MAPK, JNK, and NF-kappaB signal pathways [abstract]. 8th Avian Immunology Research Group Meeting. p. 77.

Technical Abstract: Toll-like receptor 9 (TLR9) agonist, CpG oligodeoxynucleotides (CpG-ODN), can activate the host immune system and influence the host responses to infection. In this study, a synthetic CpG-ODN was evaluated for its ability to up-regulate nitric oxide (NO) production in peripheral blood monocytes (PBMC) from neonatal chickens. Results demonstrate that CpG-ODN is a very potent stimulator, comparable to the TLR4 agonist lipopolysaccharide (LPS), for NO induction. The induction of NO by CpG-ODN required activation of mitogen-activated protein kinase (MAPK) signaling pathways, including p38 MAPK, extracellular signal-regulated kinase (ERK), and c-jun N-terminal kinase (JNK). Pretreatment of PBMC with inhibitors to p38MAPK (SB203580), ERK (U0126), JNK (SP600125), inhibited CpG-ODN induced NO production. In addition, an inhibitor (BAY 11-7082) that blocks the nuclear factor NF-kappaB inhibitory protein IkappaB phosphorylation, which in turn prevents the activation of the NF-kappaB, completely abolished NO induction by CpG-ODN. Our results demonstrated that the PBMC from neonatal chickens expresses TLR9 which recognizes CpG-ODN and initiates innate immune response.