| First Author | Poole JA | Year | 2011 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 301 |
| Issue | 3 | Pages | L296-306 |
| PubMed ID | 21665963 | Mgi Jnum | J:176330 |
| Mgi Id | MGI:5290049 | Doi | 10.1152/ajplung.00086.2011 |
| Citation | Poole JA, et al. (2011) Organic dust augments nucleotide-binding oligomerization domain expression via an NF-{kappa}B pathway to negatively regulate inflammatory responses. Am J Physiol Lung Cell Mol Physiol 301(3):L296-306 |
| abstractText | Nucleotide-binding oligomerization domain 2 (NOD2) is involved in innate immune responses to peptidoglycan degradation products. Peptidoglycans are important mediators of organic dust-induced airway diseases in exposed agriculture workers; however, the role of NOD2 in response to complex organic dust is unknown. Monocytes/macrophages were exposed to swine facility organic dust extract (ODE), whereupon NOD2 expression was evaluated by real-time PCR and Western blot. ODE induced significant NOD2 mRNA and protein expression at 24 and 48 h, respectively, which was mediated via a NF-kappaB signaling pathway as opposed to a TNF-alpha autocrine/paracrine mechanism. Specifically, NF-kappaB translocation increased rapidly following ODE stimulation as demonstrated by EMSA, and inhibition of the NF-kappaB pathway significantly reduced ODE-induced NOD2 expression. However, there was no significant reduction in ODE-induced NOD2 gene expression when TNF-alpha was inhibited or absent. Next, it was determined whether NOD2 regulated ODE-induced inflammatory cytokine production. Knockdown of NOD2 expression by small interfering RNA resulted in increased CXCL8 and IL-6, but not TNF-alpha production in response to ODE. Similarly, primary lung macrophages from NOD2 knockout mice demonstrated increased IL-6, CXCL1, and CXCL1, but not TNF-alpha, expression. Lastly, a higher degree of airway inflammation occurred in the absence of NOD2 following acute (single) and repetitive (3 wk) ODE exposure in an established in vivo murine model. In summary, ODE-induced NOD2 expression is directly dependent on NF-kappaB signaling, and NOD2 is a negative regulator of complex, organic dust-induced inflammatory cytokine/chemokine production in mononuclear phagocytes. |
