Inhibitor of p42/44 mitogen-activated protein kinase, but not p38 MAPK, attenuated antigen challenge of guinea pig airways in vitro

Chue, Sung Chian; Seow, Cherng Jye; Duan, Wei; Yeo, Leonard L.L.; Koh, A H M; Wong, W.S. Fred

doi:10.1016/j.intimp.2004.05.004

Cited by 10 publications

(6 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The infiltrated cells secrete more cytokines and inflammatory mediators, which aggravate and exacerbate the asthma (12). Studies have suggested that use of Abs against the inflammatory markers such as interleukins and leukotriene (33–35, 57–59), or inhibitors of enzymes such as COX-2 (60) or pharmacological agents that inhibit signaling kinases such as MAPK (26, 29, 31), PI-3K (27), glycogen synthase kinase-3 β (28), or inhibitors of transcription factors NF- κ B and AP-1 (30) could be helpful in the treatment of asthma. We have demonstrated that the increased expression of inflammatory markers such as IL-6, IL-8, and COX-2 at both protein and mRNA levels in SAEC in response to LPS as well as TNF- α were prevented by inhibiting AR by pharmacological inhibition as well as by genetic ablation of AR message.…”

Section: Discussionmentioning

confidence: 99%

Aldose Reductase Inhibition Suppresses the Expression of Th2 Cytokines and Airway Inflammation in Ovalbumin-Induced Asthma in Mice

Yadav¹,

Naura

Aguilera-Aguirre

et al. 2009

The Journal of Immunology

View full text Add to dashboard Cite

Airway inflammation induced by reactive oxygen species-mediated activation of redox-sensitive transcription factors is the hallmark of asthma, a prevalent chronic respiratory disease. In various cellular and animal models, we have recently demonstrated that, in response to multiple stimuli, aldose reductase (AR) regulates the inflammatory signals mediated by NF-κB. Because NF-κB-mediated inflammation is a major characteristic of asthma pathogenesis, we have investigated the effect of AR inhibition on NF-κB and various inflammatory markers in cellular and animal models of asthma using primary human small airway epithelial cells and OVA-sensitized/challenged C57BL/6 mice, respectively. We observed that pharmacological inhibition or genetic ablation of AR by small interfering RNA prevented TNF-α- as well as LPS-induced apoptosis; reactive oxygen species generation; synthesis of inflammatory markers IL-6, IL-8, and PGE2; and activation of NF-κB and AP-1 in small airway epithelial cells. In OVA-challenged mice, we observed that administration of an AR inhibitor markedly reduced airway hyperresponsiveness, IgE levels, eisonophils infiltration, and release of Th2 type cytokines in the airway. Our results indicate that AR inhibitors may offer a novel therapeutic approach to treat inflammatory airway diseases such as asthma.

show abstract

Section: Discussionmentioning

confidence: 99%

Aldose Reductase Inhibition Suppresses the Expression of Th2 Cytokines and Airway Inflammation in Ovalbumin-Induced Asthma in Mice

Yadav¹,

Naura

Aguilera-Aguirre

et al. 2009

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…To reveal these relationships we chose gefitinib which inhibits EGFR phosphorylation, PI3K/ Akt and MAPK, simultaneously. Based on previous studies (Chue et al, 2004;Lee et al, 2006a), selective Akt/PI3K or MAPK inhibitors reduce airway inflammation. In that study, they showed that airway inflammation or hyperresponsiveness are related with selective inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Potential use of an anticancer drug gefinitib, an EGFR inhibitor, on allergic airway inflammation

Hur

Lee²,

Lee³

et al. 2007

Exp Mol Med

View full text Add to dashboard Cite

The EGFR plays an essential role in goblet cell hyperplasia and mucus hypersecretion. EGFR has an intrinsic tyrosine kinase activity that, when activated, induces the production of MUC5AC through the signaling kinase cascade in the airway epithelium. We have investigated the effects of an EGFR tyrosine kinase inhibitor, gefitinib, on ovalbumin (OVA)-induced, allergic inflammation in airway epithelia of mice. OVA-sensitized mice were pretreated with gefitinib at two different doses (12.5 and 50 mg/kg) and then challenged with OVA. The OVA challenge increased the total cell count and eosinophil count in bronchoalveolar lavage fluid (BALF), as well as the concentrations of T-helper2 (Th2) cytokines, such as IL-4 and IL-13, overall eosinophil recruitment in the lung tissue and airway hyperresponsiveness (AHR). Pretreatment with gefitinib reduced the inflammatory cell counts and released cytokine concentrations (IL-4 and IL-13) in BALF, as well as eosinophil recruitment in the lungs and AHR, in a dose-dependent manner. This was associated with decreased EGFR and Akt phosphorylation. We showed that gefitnib inhibits EGFR and phosphoinositol 3'-kinase (PI3K)/Akt activation which were activated in OVA sensitized mice. These findings suggest that inhibitors of the EGFR cascade may have a role in the treatment of asthma.

show abstract

“…This suggests that the ERK signaling pathway is more important to RBL-2H3 cells under SP and/or allergen activation. A previous study showed that U0126 slightly reduced OVA-induced release of histamine but significantly inhibited the release of LTs from guinea pig lung fragments [34]. In contrast, a study with rat peritoneal mast cells showed that p38 MAPK and JNK, but not ERK, were induced 5 min after exposure to SP and the specific p38 MAPK inhibitor SB203580 abolished SP-induced increase in TNF-a and reduced histamine secretion [35].…”

Section: Discussionmentioning

confidence: 94%

Enhancement of the release of inflammatory mediators by substance P in rat basophilic leukemia RBL-2H3 cells

Liao

Hou

Wang³

et al. 2006

J Biomed Sci

View full text Add to dashboard Cite

SummarySubstance P (SP), a neurotransmitter, may play an important role in neurogenic inflammation. Ginseng has been used extensively in traditional medicine; however, few studies were focused on their anti-allergic effect. Therefore, the effect and mechanism of ginsenoside Rb1 on the SP enhancement of allergic mediators were explored. In this study, SP and dinitrophenyl-bovine serum albumin (DNP-BSA) were used to activate rat basophilic leukemia (RBL)-2H3 cells. The cultured supernatants were assayed for histamine, leukotriene C 4 (LTC 4 ) and interleulin-4 (IL-4) production. The mitogen-activated protein kinases (MAPKs) signaling pathway was determined by Western blotting analysis. We found that IgE/DNP-BSA, SP, ginsenoside Rb1, or MAPK specific inhibitors had no effect on cell viability and cytotoxicity. SP (30 lM) alone, did not induce histamine and LTC 4 release, but it enhanced allergen-induced histamine and LTC 4 release. In addition, SP significantly induced and enhanced allergen-activated IL-4. Ginsenoside Rb1 dosedependently inhibited these effects. SP enhanced the allergen-activated ERK pathway in RBL-2H3 cells, and Rb1 effectively inhibited the ERK pathway activation. Although MAPK specific inhibitors suppressed LTC 4 and IL-4, only U0126 inhibited the SP enhanced histamine release. These results demonstrate that Rb1 dose-dependently inhibited SP enhanced allergen-induced mediator release and its mechanism was through the inhibition of the ERK pathway.

show abstract

Inhibitor of p42/44 mitogen-activated protein kinase, but not p38 MAPK, attenuated antigen challenge of guinea pig airways in vitro

Cited by 10 publications

References 29 publications

Aldose Reductase Inhibition Suppresses the Expression of Th2 Cytokines and Airway Inflammation in Ovalbumin-Induced Asthma in Mice

Aldose Reductase Inhibition Suppresses the Expression of Th2 Cytokines and Airway Inflammation in Ovalbumin-Induced Asthma in Mice

Potential use of an anticancer drug gefinitib, an EGFR inhibitor, on allergic airway inflammation

Enhancement of the release of inflammatory mediators by substance P in rat basophilic leukemia RBL-2H3 cells

Contact Info

Product

Resources

About