The role of Src & ERK1/2 kinases in inspiratory resistive breathing induced acute lung injury and inflammation.

Background: Inspiratory resistive breathing (IRB), a hallmark of obstructive airway diseases, is associated with large negative intrathoracic pressures, due to strenuous contractions of the inspiratory muscles. IRB is shown to induce lung injury in previously healthy animals. Src is a multifunctional kinase that is activated in the lung by mechanical stress.

Inspiratory resistive breathing induces MMP-9 and MMP-12 expression in the lung.

Inspiratory resistive breathing (IRB) is characterized by large negative intrathoracic pressures and was shown to induce pulmonary inflammation in previously healthy rats. Matrix metalloproteinases (MMP)-9 and -12 are induced by inflammation and mechanical stress in the lung. We hypothesized that IRB induces MMP-9 and -12 in the lung.

Inspiratory resistive breathing induces acute lung injury.

Rationale: Resistive breathing is associated with large negative intrathoracic pressures. Increased mechanical stress induces high-permeability pulmonary edema and lung inflammation.

Objectives: To determine the effects of resistive breathing on the healthy lung.

Nitric oxide stimulates interleukin-6 production in skeletal myotubes.

Strenuous exercise leads to the up-regulation of interleukin-6 (IL-6) production and enhanced nitric oxide (NO) release within the contracting skeletal muscles. In this study, we investigated whether NO regulates IL-6 production in C2C12 myotubes. These cells exhibited a concentration-dependent increase in IL-6 production upon stimulation with NO donors (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NONOate), (Z)-1-[N-(3-aminopropyl)-N-(n-propyl)amino]diazen-1-ium-1,2-diolate (PAPA-NONOate), and sodium nitroprusside (SNP).

The complement inhibitor CD59 and the lymphocyte function-associated antigen-3 (LFA-3, CD58) genes possess functional binding sites for the p53 tumor suppressor protein.

p53 is an oncosuppressor protein, which acts via transcriptional and non-transcriptional mechanisms. The transcriptional function of p53 is mediated by specific responsive elements. In the present study we found active responsive elements, specific for the p53 within the 5'flanking region and within the first intron of the gene encoding for the CD59 membrane inhibitor of reactive lysis, and within the first intron of the gene encoding for the CD58 membrane protein (LFA-3).