Chenodeoxycholic acid attenuates ovalbumin-induced airway inflammation in murine model of asthma by inhibiting the T(H)2 cytokines.

Asthma is a complex highly prevalent airway disease that is a major public health problem for which current treatment options are inadequate. Recently, farnesoid X receptor (FXR) has been shown to exert anti-inflammatory actions in various disease conditions, but there have been no reported investigations of Chenodeoxycholic acid (CDCA), a natural FXR agonist, in allergic airway inflammation. To test the CDCA effectiveness in airway inflammation, ovalbumin (OVA)-induced acute murine asthma model was established. We found that lung tissue express FXR and CDCA administration reduced the severity of the murine allergic airway disease as assessed by pathological and molecular markers associated with the disease. CDCA treatment resulted in fewer infiltrations of cells into the airspace and peribronchial areas, and decreased goblet cell hyperplasia, mucus secretion and serum IgE levels which was increased in mice with OVA-induced allergic asthma. The CDCA treatment further blocked the secretion of TH2 cytokines (IL-4, IL-5 and IL-13) and proinflammatory cytokine TNF-α indicate that the FXR and its agonists may have potential for treating allergic asthma.

Role of farnesoid X receptor in inflammation and resolution.

OBJECTIVE: The aim of this paper is to review the developments of farnesoid X receptor (FXR) biology, its ligands, and various functions, in particular we discuss the anti-inflammatory and anti-fibrotic role in chronic inflammatory diseases. INTRODUCTION: FXR is a ligand-dependent transcription factor belonging to the nuclear hormone receptor superfamily. The accrued data have shown that the FXR plays important roles not only in bile acid, lipid metabolism, and carbohydrate homeostasis, but also in inflammatory responses. The anti-inflammatory and anti-fibrotic effects of FXR on chronic inflammatory diseases are not well documented. METHODS: A literature survey was performed using PubMed database search to gather complete information regarding FXR and its role in inflammation. RESULTS AND DISCUSSION: FXR is highly expressed in liver, intestine, kidney and adrenals, but with lower expression in fat tissue, heart and recently it has been found to express in lungs too. Primary bile acids, cholic acid and chenodeoxycholic acid are the natural endogenous ligands for FXR. GW4064 and 6α-ethyl-chenodeoxycholic acid are the synthetic high-affinity agonists. An exhaustive literature survey revealed that FXR acts as a key metabolic regulator and potential drug target for many metabolic syndromes that include chronic inflammatory diseases.

The role of nitrated fatty acids and peroxisome proliferator-activated receptor gamma in modulating inflammation.

Nitrated fatty acids (NFAs), thought to be produced by nonenzymatic reactions of endogenous nitric oxide (NO) with naturally present unsaturated fatty acids, have recently been identified as one of the largest single pools of biologically active NO derivatives in human plasma. As the biological role of NFAs is unknown, initial in vitro studies have shown them to be potent suppressors of inflammatory responses. The aim of the study was to collect all the literature on NFAs and its interactions with peroxisome proliferator-activated receptor gamma (PPAR-γ) and review in detail the anti-inflammatory properties of PPAR-γ interceded by NFAs. A literature survey was performed using PubMed and ScienceDirect to gather complete information on NFAs and their interactions with PPAR-γ. An exhaustive literature survey revealed that NFAs found in human plasma and urine comprises a class of cell signaling mediators that can activate PPAR-γ within its physiological concentration. NFAs exhibit anti-inflammatory and anti-fibrotic effects through PPAR-γ activation in various in vitro models tested. Besides its role in inflammation other properties of NFAs such as inhibition of enzymes, inducer of gene expression, etc., were discussed. NFAs are good electrophiles with pleiotropic biological activities. Hence NFAs can be treated as potent drug candidates.