ABSTRACT
Low-level laser therapy (LLLT) controls bronchial hyperresponsiveness (BHR) associated with increased RhoA expression as well as pro-inflammatory mediators associated with NF-kB in acute lung inflammation. Herein, we explore if LLLT can reduce both BHR and Th2 cytokines in allergic asthma. Mice were studied for bronchial reactivity and lung inflammation after antigen challenge. BHR was measured through dose-response curves to acetylcholine. Some animals were pretreated with a RhoA inhibitor before the antigen. LLLT (660 nm, 30 mW and 5.4 J) was applied on the skin over the right upper bronchus and two irradiation protocols were used. Reduction of BHR post LLLT coincided with lower RhoA expression in bronchial muscle as well as reduction in eosinophils and eotaxin. LLLT also diminished ICAM expression and Th2 cytokines as well as signal transducer and activator of transduction 6 (STAT6) levels in lungs from challenged mice. Our results demonstrated that LLLT reduced BHR via RhoA and lessened allergic lung inflammation via STAT6.
Subject(s)
Airway Remodeling/radiation effects , Asthma/radiotherapy , Bronchoconstriction/radiation effects , Cytokines/metabolism , Hypersensitivity/radiotherapy , Low-Level Light Therapy , Airway Remodeling/drug effects , Airway Remodeling/physiology , Amides/pharmacology , Animals , Asthma/drug therapy , Asthma/physiopathology , Bronchi/drug effects , Bronchi/physiopathology , Bronchi/radiation effects , Bronchial Hyperreactivity/drug therapy , Bronchial Hyperreactivity/physiopathology , Bronchial Hyperreactivity/radiotherapy , Bronchoconstriction/drug effects , Bronchoconstriction/physiology , Enzyme Inhibitors/pharmacology , Hypersensitivity/drug therapy , Hypersensitivity/physiopathology , Lung/drug effects , Lung/physiopathology , Lung/radiation effects , Male , Mice , Mice, Inbred BALB C , Muscle, Smooth/drug effects , Muscle, Smooth/physiopathology , Muscle, Smooth/radiation effects , Ovalbumin/adverse effects , Pneumonia/drug therapy , Pneumonia/physiopathology , Pneumonia/radiotherapy , Pyridines/pharmacology , STAT6 Transcription Factor/metabolism , rho GTP-Binding Proteins/antagonists & inhibitors , rho GTP-Binding Proteins/metabolism , rhoA GTP-Binding ProteinABSTRACT
Oxidative stress is present in severe asthma and contributes to the low response to corticoids through the downregulation of histone deacetylase (HDAC) and the increase of cytokines. Low-level laser therapy (LLLT) has been proven to be an anti-inflammatory. Thus, we investigated the laser effect on lipopolysaccharide (LPS)-induced cytokine secretion and HDAC activity in U937 cells under oxidative stress. U937 cells activated with oxidative stress were treated with dexamethasone (dexa) or laser. Cytokines and phosphoinositide 3-kinase (PI3K) were measured by ELISA whilst the HDAC was detected through colorimetric assay. LPS activated- U937 cells cytokines secretion increased with H2O2 (hydrogen peroxide) as well as with TSA (trichostatin). The HDAC activity in activated U937 cells was decreased. LLLT and dexa inhibited the LPS-stimulated U937 cells cytokines, but dexa effect disappeared with H2O2. With TSA, the LLLT was less effective on H2O2/LPS stimulated- U937 cells cytokines. Dexa failed on H2O2/LPS- induced HDAC, while LLLT restored the HDAC and the dexa effect. LLLT plus prostaglandin E2 (PGE2) increased cyclic adenosine monophosphate (cAMP) and potentiated the laser action on oxidative stress-induced cytokine. LLLT reduced the PI3K and its effects on cytokine and HDAC was suppressed with LY294002. In situations of corticoid resistance, LLLT acts decreasing the cytokines and HDAC through the activation of the protein kinase A via the inhibition of PI3K.
