Dietary Fatty Acids Amplify Inflammatory Responses to Infection through p38 MAP Kinase Signaling.

Publication Type:
Journal Article
Am J Respir Cell Mol Biol, 2019
Issue Date:
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Obesity is an important risk factor for severe asthma exacerbations, which are mainly caused by respiratory infections. Dietary fatty acids, which are increased systemically in obese patients and are further increased after high fat meals, affect the innate immune system and may contribute to dysfunctional immune responses to respiratory infection. This study investigated the effects of dietary fatty acids on immune responses to respiratory infection in pulmonary fibroblasts and a bronchial epithelial cell line (BEAS-2B). Cells were challenged with BSA-conjugated fatty acids (ω-6 PUFAs, ω-3 PUFAs or SFAs) +/- the viral mimic polyinosinic:polycytidylic acid (PolyI:C) or bacterial compound lipoteichoic acid (LTA) and release of pro-inflammatory cytokines was measured. In both cell types, challenge with arachidonic acid (AA) (ω-6 PUFA) and PolyI:C or LTA led to substantially greater IL-6 and CXCL8 release than either challenge alone, demonstrating synergy. In epithelial cells, palmitic acid (SFA) combined with PolyI:C also led to greater IL-6 release. The underlying signaling pathways of AA and PolyI:C -or LTA-induced cytokine release were examined using specific signaling inhibitors and immunoblotting. Cytokine production in pulmonary fibroblasts was prostaglandin-dependent, and synergistic upregulation occurred via p38 MAP kinase signaling, whereas cytokine production in BEAS2Bs was mainly mediated through JNK and p38 MAPK signaling. We confirmed these findings using rhinovirus infection, demonstrating that AA enhances rhinovirus-induced cytokine release. This study suggests that during respiratory infection, increased levels of dietary ω-6 PUFAs and SFAs may lead to more severe airway inflammation and may contribute to and/or increase the severity of asthma exacerbations.
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