Spleen tyrosine kinase inhibition blocks airway constriction and protects from Th2-induced airway inflammation and remodeling.

BACKGROUND: Spleen tyrosine kinase (Syk) is an intracellular nonreceptor tyrosine kinase, which has been implicated as central immune modulator promoting allergic airway inflammation. Syk inhibition has been proposed as a new therapeutic approach in asthma. However, the direct effects of Syk inhibition on airway constriction independent of allergen sensitization remain elusive. METHODS: Spectral confocal microscopy of human and murine lung tissue was performed to localize Syk expression. The effects of prophylactic or therapeutic Syk inhibition on allergic airway inflammation, hyperresponsiveness, and airway remodeling were analyzed in allergen-sensitized and airway-challenged mice. The effects of Syk inhibitors BAY 61-3606 or BI 1002494 on airway function were investigated in isolated lungs of wild-type, PKCα-deficient, mast cell-deficient, or eNOS-deficient mice. RESULTS: Spleen tyrosine kinase expression was found in human and murine airway smooth muscle cells. Syk inhibition reduced allergic airway inflammation, airway hyperresponsiveness, and pulmonary collagen deposition. In naïve mice, Syk inhibition diminished airway responsiveness independently of mast cells, or PKCα or eNOS expression and rapidly reversed established bronchoconstriction independently of NO. Simultaneous inhibition of Syk and PKC revealed additive dilatory effects, whereas combined inhibition of Syk and rho kinase or Syk and p38 MAPK did not cause additive bronchodilation. CONCLUSIONS: Spleen tyrosine kinase inhibition directly attenuates airway smooth muscle cell contraction independent of its protective immunomodulatory effects on allergic airway inflammation, hyperresponsiveness, and airway remodeling. Syk mediates bronchoconstriction in a NO-independent manner, presumably via rho kinase and p38 MAPK, and Syk inhibition might present a promising therapeutic approach in chronic asthma as well as acute asthma attacks.

A study on some physical attributes of Naeini sheep wool for textile industry.

In order to evaluate some physical and qualitative characteristics of Naeini sheep wool for using in textile industry, herds from 6 different regions of Isfahan province were chosen. Staple length from 3 different body parts (shoulder, side and britch) was measured prior to shearing. Wool samples were taken from a 100 cm2 surface on the mid-side of the Animals. Then the samples were transferred to the Laboratory of Animal Sciences for evaluations of some quality characteristics and to the Fiber Physics Laboratory for measuring tenacity, breaking strength and elongation at break of fibers. The means and standard deviations of staple length were estimated (10.8 +/- 2.36), (9.71 +/- 3.14) and (10.99 +/- 2.49) cm for shoulder, side and britch parts, respectively. The total average staple length of Naeini sheep (10.5 cm) is suitable for using in textile industry. Wool fibers of Naeini sheep have desirable tenacity and breaking strength (1.22 cN/dtex and 13.76 centi-Newton) to resist against mechanical tensions of the spinning step. However, Naeini sheep wool fibers have an adequate, but not a desirable % elongation at break (28.6%). Based on the fiber diameter mean of Naeini sheep and its variation (28.51 +/- 4.33 microm) the fleece grade of Naeini sheep was predicted 54's, which is an intermediate grade. However, by conducting breeding programs toward enhancing fleece grade, Naeini sheep wool will be simply applicable in textile industry.