Molecular basis of chronic inflammation in lung diseases: new therapeutic approach.
There is increasing evidence that histone acetylation, controlled by histone acetyltransferases (HAT), reversed by histone deacetylases (HDAC) plays a critical role in the process of regulation of inflammatory genes and in mediating the anti-inflammatory effects of corticosteroids in asthma patients. There is evidence of an increase in HAT activity in asthmatics, which leads to increased expression of multiple inflammatory genes that are regulated by proinflamatory factors, such as nuclear factor NF-kappaB. Reduction in HDAC activity, secondary to oxidative and nitrative stress and severe inflammation, may account for the amplified inflammation in chronic obstructive pulmonary disease (COPD). Corticosteroids switch off inflammatory genes through the inhibition of HAT activity and by recruitment of HDAC2 to the activated transcription complex. Several new strategies to control inflammations in COPD, aiming at restoration of the HDAC-2 activity and/or mitigation of HAT-related signaling are in the preclinical and clinical development.
Mroz
R M
RM
Department of Pneumology, Bialystok Medical University, Bialystok, Poland. robmroz@wp.pl
Noparlik
J
J
Chyczewska
E
E
Braszko
J J
JJ
Holownia
A
A
D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000201:enzymology; D002908:Chronic Disease; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology; D011014:Pneumonia / Q000188:drug therapy* / Q000201:enzymology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000201:enzymology
D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases