MAPKs and NF-kappa B differentially regulate cytokine expression in the diaphragm in response to resistive breathing: the role of oxidative stress

作者：Sigala Ioanna; Zacharatos Panayiotis; Toumpanakis Dimitris; Michailidou Tatiana; Noussia Olga; Theocharis Stamatios; Roussos Charis; Papapetropoulos Andreas; Vassilakopoulos Theodoros^*

来源：American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, 2011, 300(5): R1152-R1162.

DOI：10.1152/ajpregu.00376.2010

• exercise
• inflammation
• respiratory muscles
• skeletal muscle

Sigala I, Zacharatos P, Toumpanakis D, Michailidou T, Noussia O, Theocharis S, Roussos C, Papapetropoulos A, Vassilakopoulos T. MAPKs and NF-kappa B differentially regulate cytokine expression in the diaphragm in response to resistive breathing: the role of oxidative stress. Am J Physiol Regul Integr Comp Physiol 300: R1152-R1162, 2011. First published February 16, 2011; doi:10.1152/ajpregu.00376.2010.-Inspiratory resistive breathing (IRB) induces cytokine expression in the diaphragm. The mechanism of this cytokine induction remains elusive. The roles of MAPKs and NF-kappa B and the impact of oxidative stress in IRB-induced cytokine upregulation in the diaphragm were studied. Wistar rats were subjected to IRB (50% of maximal inspiratory pressure) via a two-way nonrebreathing valve for 1, 3, or 6 h. Additional groups of rats subjected to IRB for 6 h were randomly assigned to receive either solvent or N-acetyl-cysteine (NAC) or inhibitors of NF-kappa B (BAY-11-7082), ERK1/2 (PD98059), and P38 MAPK (SB203580) to study the effect of oxidative stress, NF-kappa B, and MAPKs in IRB-induced cytokine upregulation in the diaphragm. Quietly breathing animals served as controls. IRB upregulated cytokine (IL-6, TNF-alpha, IL-10, IL-2, IL-1 beta) protein levels in the diaphragm and resulted in increased activation of MAPKs (P38, ERK1/2) and NF-kappa B. Inhibition of NF-kappa B and ERK1/2 blunted the upregulation of all cytokines except that of IL-6, which was further increased. P38 inhibition attenuated all cytokine (including IL-6) upregulation. Both P38 and ERK1/2 inhibition decreased NF-kappa B/p65 subunit phosphorylation. NAC pretreatment blunted IRB-induced cytokine upregulation in the diaphragm and resulted in decreased ERK1/2, P38, and NF-kappa B/p65 phosphorylation. In conclusion, IRB-induced cytokine upregulation in the diaphragm is under the regulatory control of MAPKs and NF-kappa B. IL-6 is regulated differently from all other cytokines through a P38-dependent and NF-kappa B independent pathway. Oxidative stress is a stimulus for IRB-induced cytokine upregulation in the diaphragm.

• 出版日期2011-5