Cysteinyl leukotriene receptor antagonist regulates allergic airway inflammation in an organ- and cytokine-specific manner

نویسندگان

  • Tetsuya Kawano
  • Hiroto Matsuse
  • Tomoko Tsuchida
  • Susumu Fukahori
  • Chizu Fukushima
  • Tomoya Nishino
  • Shigeru Kohno
چکیده

BACKGROUND Cysteinyl leukotrienes (cys-LTs) are very important factors in the pathophysiology of bronchial asthma. Cys-LT receptor antagonists (LTRAs) decrease allergic airway inflammation. The aim of the present study was to determine the differential effects of LTRAs and corticosteroids on allergic airway inflammation and allergen-specific cytokine production from lymphoid tissues using a murine model of asthma. MATERIAL AND METHODS Four groups of female BALB/c mice [control (Cont); Dermatophagoides farinae allergen-sensitized (AS); pranlukast (Prl), an LTRA-treated AS; and dexamethasone (Dex)-treated AS] were examined. Lung pathology and cytokine production by prepared mononuclear cells isolated from mediastinal lymph nodes (MLNs) and spleen were compared among these groups. RESULTS AS mice exhibited allergic airway inflammation and significant increases in allergen-specific Th1 and Th2 cytokines in MLNs and spleen. Prl-treated mice showed significant attenuation of allergic airway inflammation concomitant with reduction of Th2 cytokines and IFN-g in MLNs but not in spleen. In contrast, Dex significantly decreased Th1 and Th2 cytokines in MLNs and also decreased them (except IL-13 and IL-2) in spleen. CONCLUSIONS The inflammatory effects of cys-LTs could differ in lymphoid organs. LTRAs potentially regulate allergic airway inflammation in an organ- and cytokine-specific manner, while systemic corticosteroid shows nonspecific effects.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

The administration of clopidogrel attenuates airway hyperresponsiveness and airway inflammation in an ovalbumin specific allergic asthma model

Background and objective Cysteinyl leukotrienes (LTs) contribute to airway inflammation by interacting with type 1 and 2 cysteinyl leukotriene receptors as well as not clearly known type 3 leukotriene receptors. In contrast to LTC4 and LTD4, LTE4 is weak agonist at type 1 and 2 cysteinyl leukotriene receptors. Although LTE4 plays a key role in airway inflammation, our understanding of its poten...

متن کامل

Role of leukotriene receptor antagonists in asthma.

Asthma is a chronic inflammatory disease that affects >300 million people worldwide. However, inhaled corticosteroids (ICS), the gold standard therapy for persistent asthma, cannot suppress every component of airway inflammation and often fail to adequately penetrate the small airways in order completely suppress eosinophilia. Cysteinyl leukotrienes are important inflammatory factors that are i...

متن کامل

The epidermal growth factor receptor mediates allergic airway remodelling in the rat.

The chronicity of bronchial asthma is attributed to persistent airway inflammation and to a variety of structural changes, or remodelling, that includes smooth muscle and goblet cell hyperplasia. To investigate the mechanisms of airway remodelling, the current authors used an established allergen (ovalbumin; OVA)-driven rodent model (the Brown Norway rat). Brown Norway rats were sensitised to O...

متن کامل

Effects of montelukast (MK-0476); a potent cysteinyl leukotriene receptor antagonist, on bronchodilation in asthmatic subjects treated with and without inhaled corticosteroids.

BACKGROUND Cysteinyl leukotriene release in association with airway inflammation is a feature of clinical asthma. The acute effects of montelukast (MK-0476), a potent, orally administered, specific cysteinyl leukotriene receptor antagonist, on airways obstruction was assessed in patients with mild to moderately severe asthma. METHODS Twenty two asthmatic subjects were randomised to receive mo...

متن کامل

Leukotriene E4 activates human Th2 cells for exaggerated proinflammatory cytokine production in response to prostaglandin D2.

PGD(2) exerts a number of proinflammatory responses through a high-affinity interaction with chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) and has been detected at high concentrations at sites of allergic inflammation. Because cysteinyl leukotrienes (cysLTs) are also produced during the allergic response, we investigated the possibility that cysLTs may modulate the...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 20  شماره 

صفحات  -

تاریخ انتشار 2014