[Effect and mechanism of IL-1ß/JNK transduction pathway on the nasal mucosa remodeling in allergic rhinitis rats].

OBJECTIVE: To study the role of JNK (c-Jun N-terminal kinase) signal transduction pathway on the nasal mucosa remodeling in allergic rhinitis rats, to explore whether IL-1ß participates the nasal mucosa remodeling in allergic rhinitis by JNK signal transduction pathway. METHOD: Totally 60 male Wistar rats (weighing about 200-250 g)were randomly divided into A (AR group) and B group (control group). The rats in A group were sensitized for inducing AR by intraperitoneal injection ovalbumin and Al(OH)3. Ovalbumin was respectively dropped in each nasal cavity of every rat for 4,8,12 weeks(A4,A8,or A12 group) each had 10 rats. The rats in B group were sensitized by intraperitoneal injection saline. Saline was respectively dropped in each nasal cavity of every rat for 4,8, 12 weeks(B4, B8, or B12 group), and each had 10 rats. The concentration of IL-1ß in serum and nasal lavage fluid were tested by ELASA. The protein expressions of P-JNK and P-c-Jun were detected by immunohistochemical technique. Linear correlation analysis showed the correlation between levels of IL-1ß in serum and P-JNK protein, levels of IL-1ß in nasal lavage fluid and P-JNK protein. RESULT: The concentrations of IL-1ß in serum and nasal lavage fluid of A group were all significantly higher than those of the corresponding B group (all P < 0.01). Compared with A4 group and A8 group, concentrations of IL-1ß in nasal lavage fluid of A12 group were significantly increased (all P < 0.01). However the levels of IL-1ß in serum were not significantly different among them (all P > 0.05). Mean absorbance values of P-JNK and P-c-Jun in A group were significantly higher than those in corresponding B group (all P < 0.01) and compared with A4 group and A8 group, those of A12 group were significantly increased (all P < 0.01). Strong positive correlation were found between P-JNK and concentration of IL-1ß in serum or nasal lavage fluid (r = 0.835 and r = 0.902, all P < 0.01). CONCLUSION: JNK signal transduction pathway plays important role in the nasal mucosa remodeling in allergic rhinitis rats. IL-1ß participates in AR nasal mucosa remodeling possibly partly through activating JNK signal transduction pathway.

[Role of P-JNK and P-c-Jun of JNK transduction pathway on the nasal mucosa remodeling in allergic rhinitis rats].

OBJECTIVE: To study the role of P-JNK and P-c-Jun of JNK (c-Jun N-terminal kinase) on nasal mucosa remodeling in allergic rhinitis rats. METHOD: Sixty male Wistar rats (weighing about 200-250 g) were randomly divided into AR group (A group) and B group(control group). The rats in A group were sensitized for inducing AR by intraperitoneal injection of ovalbumin and Al(OH)3. Rats in group A were randomized into A4, A8 and A12 group (each had 10 rats). Ovalbumin was dropped in each nasal cavity of every rat for 4,8,12 weeks, respectively. Rats in group B were sensitized by saline instead of OVA, and were also divided into B4, B8 and B12 group. Each group had 10 rats. Pathological changes of nasal mucosa in each period were observed by hematoxylin and eosin stain dyeing. The phosphorylation of JNK and c-Jun were tested by immunohistochemistry. RESULT: In A8 group, mucosal congestion and edema thickening with inflammatory cells infiltration of eosinophils were observed in the eighth week, and the inflammatory changes were significantly increased as time went on. The mean absorbance values of P-JNK and P-c-Jun in A group were significantly higher than those in the corresponding B group (all P < 0.01). Moreover, the mean absorbance values of A12 group were significantly higher than A4 group and A8 group (all P < 0.01 ). CONCLUSION: The expression of P-JNK and P-c-Jun in the process of nasal mucosa remodeling in allergic rhinitis rats were increased, which suggested that P-JNK and P-c-Jun played important roles in nasal mucosa remodeling of the allergic rhinitis rats.

[Effects of intranasal interferon gamma on transforming growth factor-ß1/Smad in rats with allergic rhinitis].

OBJECTIVE: To investigate the effects of intranasal interferon gamma (IFN-γ) on nasal mucosa remodeling and expression of transforming growth factor-ß1 (TGF-ß1), Smad2, Smad3, Smad7 in allergic rhinitis (AR) rat model. METHODS: Ovalbumin (OVA) and aluminum hydroxide were used to construct the AR model. Thirty AR rats were randomly divided into positive control group (group B, n = 10), IFN-γ treatment group (group C, n = 10) and negative control group (normal rats, n = 10). After the AR models were built, 50 µl PBS, 1 µg IFN-γ was dropped into the nasal cavity of each rat in group B and group C, from the fouth week to tenth week, twice a week. The nasal mucosa was collected on day 71 in order to observe the pathologic changes, and the expression of TGF-ß1, TGF-ß1 mRNA, Smad2 mRNA, Smad3 mRNA and Smad7 mRNA by immunohistochemistry and reverse transcriptase-polymerase chain reaction. RESULTS: Decreases of TGF-ß1, Smad2 and Smad3 mRNA were seen in nasal tissue of group C (0.59 ± 0.04, 0.39 ± 0.08, 0.46 ± 0.15) as compared with group B (0.82 ± 0.12, 0.70 ± 0.18, 0.95 ± 0.26), the differences were significant (q value were 3.15, 4.47, 3.03, all P < 0.05). The levels of Smad7 mRNA expression increased significantly (q = 2.98, P < 0.05) in group C (0.31 ± 0.05) as compared with group B (0.25 ± 0.06). Immunohistochemistry showed significant decrease of TGF-ß1 expression in the nasal tissue of group C much lesser than that in group B. CONCLUSIONS: Intranasal IFN-γ could decrease the expression of TGF-ß1, TGF-ß1 mRNA, Smad2 mRNA, Smad3 mRNA, increase the expression of Smad7 mRNA in AR rats model and inhibit the nasal mucosa remodeling.

[Expression and clinical significance of SHP2 in the tumor tissues of smokers with lung cancer].

BACKGROUND AND OBJECTIVE: It has been proved that protein phosphorylation and dephosphorylation were important mechanisms in lung cancer development, and tobacco smoking is an important risk factor of lung cancer. The aim of this study is to investigate the expression and clinical significance of protein tyrosine phosphatase SHP2 in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC); the relationship between tobacco smoking and the expression of SHP2 is also studied. METHODS: Immunohistochemistry (Invision) and fluorescence in situ hybridization (FISH) were used to detect the expression of SHP2 and the augment of SHP2 mRNA in the 53 lung cancer specimens. RESULTS: The weak positive rate of SHP2 was 80% (which was also the total positive rate) in normal bronchial epithelium. The weak, moderate and strong positive rates were 35.4%, 43.8% and 6.2% (total positive rate was 85.4%) in 48 NSCLC patients, 0%, 80% and 20% (total positive rate was 100%) in 5 SCLC patients, 40.7%, 37.4% and 3.7% (total positive rate was 81.5%) in the tumor tissues of 27 NSCLC patients who didn't smoke and 23.8%, 71.4% and 4.7% (total positive rate was 100%) in the tumor tissues of 21 NSCLC patients whose smoking indexes were ≥ 400. Significant differences of SHP2 expression were observed between tumor tissues and normal bronchial epithelium, NSCLC and SCLC, and between different smoking indexes (P<0.05). CONCLUSIONS: The enhancement of SHP2 expression in the tumor tissues of NSCLC patients who smoke may be correlated with tobacco smoking; SHP2 may play certain role in the development of lung cancer; SHP2 prospectively provides new ideas for the drug research and development of lung cancer treatment.

[Treatment of allergic rhinitis rats by intranasal interferon gamma].

OBJECTIVE: To investigate the effects and mechanism of intranasal interferon gamma (IFN-gamma) in the treatment of allergic rhinitis. METHODS: Ovalbumin (OVA) absorbed to aluminum hydroxide was used to construct the allergic rhinitis model (group C), and the normal control group (group A), the allergic rhinitis model group (group B) and beclomethasone dipropionate group (group D) consisted of 8 rats for each. PBS 50 microl was absorbed to group B, IFN-gamma 1 microg was absorbed to group C and beclomethasone dipropionate 3.5 microg was absorbed to group D on day 31 to day 38 once daily once nasal cavity. The nasal lavage fluid was collected on day 39, and the cellular constituents, levels of interleukin-4 (IL-4), interleukin-5 (IL-5) and IgE were determined, together with the pathologic changes and expression of GATA-3 were observed. RESULTS: Decrease of eosinophils [(0.005 +/- 0.003) x 10(4)/ml, x +/- s] was seen in nasal lavage fluid of group C as comparing with group B [(0.225 +/- 0.060) x 10(4)/ml, (P < 0.01)], and the levels of IL-4 (7.8 +/- 3.5) pg/ml and IL-5 (12.5 +/- 4.3) pg/ml decreased significantly in comparing with group B (P < 0.01). The serum levels of total IgE (38.5 +/- 9.6) microg/ml and ovalbumin-specific IgE (19.8 +/- 5.4) IU/ml decreased significantly in comparing with those of group B (P < 0.01). In group B, mucosal congestion and edema thickening with inflammatory cells infiltration mainly of eosinophils; in group C, the above mentioned changes were much more ameliorated. Immunohistochemistry showed significant increase of GATA-3 expression in the nasal tissue of group B but much lesser than that in group C. CONCLUSIONS: IFN-gamma can inhibit the composition of IL-4 and IL-5, and inhibit the airway inflammation with eosinophilic infiltration and the serum levels of total IgE and ovalbumin specific IgE, probably through the mechanism of restraining the Th2 reaction by blockade of GATA-3 expression in the nasal tissue.