Cigarette smoke extract induces cytosolic phospholipase A2 expression via NADPH oxidase, MAPKs, AP-1, and NF-κB in human tracheal smooth muscle cells

Lin

Journal Cellular Physiology

et al. 2011

Self Cite

Cytosolic phospholipase A(2) (cPLA(2)) plays a pivotal role in mediating agonist-induced arachidonic acid (AA) release for prostaglandin (PG) synthesis during inflammation triggered by tumor necrosis factor-α (TNF-α). However, the mechanisms underlying TNF-α-induced cPLA(2) expression and PGE(2) synthesis in human tracheal smooth muscle cells (HTSMCs) remain unknown. Here, we report that TNF-α-induced cPLA(2) protein and mRNA expression, PGE(2) production, and phosphorylation of p42/p44 MAPK, p38 MAPK, and JNK1/2, which were attenuated by pretreatment with a ROS scavenger [N-acetyl-L-cysteine, (NAC)] and the inhibitors of NADPH oxidase [apocynin (APO) and diphenyleneiodonium chloride (DPI)], MEK1/2 (U0126), p38 MAPK (SB202190), and JNK1/2 (SP600125) or transfection with siRNA of Nox2, p47(phox) , MEK1, p42, p38, or JNK2. TNF-α-induced cPLA(2) expression was also inhibited by pretreatment with a selective NF-κB inhibitor [helenalin (HLN)] or transfection with dominant negative mutants of NF-κB inducing kinase (NIK) or IκB kinase (IKK)α/β. TNF-α-induced NF-κB translocation was blocked by pretreatment with NAC, DPI, APO, or HLN, but not by U0126, SB202190, or SP600125. In addition, pretreatment with curcumin (a p300 inhibitor) or transfection with p300 siRNA blocked cPLA(2) expression and PGE(2) synthesis induced by TNF-α. We further confirmed that p300 was associated with the cPLA(2) promoter which was dynamically linked to histone H4 acetylation stimulated by TNF-α, determined by chromatin immunoprecipitation assay. Association of p300 and histone H4 to cPLA(2) promoter was inhibited by U0126, SB202190, and SP600125. These results suggested that in HTSMCs, activation of p47(phox) , MAPKs, NF-κB, and p300 is essential for TNF-α-induced cPLA(2) expression and PGE(2) release.

“…ROS has been shown to regulate cPLA 2 expression in HTSMCs (Cheng et al, 2009). In previous study, we have shown that Nox2 was expressed on the membrane of HTSMCs (Cheng et al, 2010).…”

Section: Tnf-a Induces Cpla 2 Expression and Pge 2 Releasementioning

confidence: 73%

“…ROS has been shown to regulate MAPKs and NF-kB activation in HTSMCs (Cheng et al, 2009(Cheng et al, , 2010. We further The RNA samples were analyzed by RT-PCR for the levels of cPLA 2 mRNA.…”

Section: Tnf-a Induces Cpla 2 Expression and Pge 2 Releasementioning

confidence: 99%

Activation and induction of cytosolic phospholipase A₂ by TNF‐α mediated through Nox2, MAPKs, NF‐κB, and p300 in human tracheal smooth muscle cells

Lin

Journal Cellular Physiology

et al. 2011

Self Cite

The American Journal of Pathology

“…[57][58][59] The available anti-inflammatory agents have limited efficacy. NF-B activation, which is induced by cigarette smoke, 60,61 is generally thought to be proinflammatory, [15][16][17][18] but researchers 7,20 -22 have shown that RelB has anti-inflammatory properties. We hypothesized that transient overexpression of the NF-B family member, RelB, in the airways of mice would dampen the proinflammatory effects of cigarette smoke and offer a potential new therapy against lung inflammation.…”

Section: Discussionmentioning

confidence: 99%

Lung-Targeted Overexpression of the NF-κB Member RelB Inhibits Cigarette Smoke–Induced Inflammation

McMillan

Baglole

Thatcher

et al. 2011

Acute lung inflammation can be caused by a variety of respirable agents, including cigarette smoke. Longterm cigarette smoke exposure can cause chronic obstructive pulmonary disease (COPD), a serious illness that affects >10 million Americans. Cigarette smoke is a known inducer of inflammation and is responsible for approximately 90% of all COPD cases. RelB, a member of the NF-B family, attenuates cigarette smoke-induced inflammatory mediator production in mouse lung fibroblasts in vitro. We hypothesized that overexpression of RelB in the airways of mice would dampen acute smoke-induced pulmonary inflammation. Mice received a recombinant adenovirus encoding RelB by intranasal aspiration to induce transient RelB overexpression in the lungs and were subsequently exposed to mainstream cigarette smoke. Markers of inflammation were analyzed after smoke exposure. Neutrophil infiltration, normally increased by smoke exposure, was significantly and potently decreased after RelB overexpression. Cigarette smoke-induced proinflammatory cytokine and chemokine production, cyclooxygenase-2 expression, and prostaglandin E 2 production were also significantly decreased in the context of RelB overexpression. The expression of intercellular adhesion molecule 1, an NF-B-dependent protein, was decreased, indicating a potential mechanism through which RelB can regulate inflammatory cell migration. Therefore, increased expression and/or activation of RelB could be a novel therapeutic strategy against acute lung inflammation caused by respirable agents and possibly against chronic injury, such as COPD.

Mustafa Kemal Üniversitesi Tıp Dergisi

“…Sigara dumanının, inflamasyon mekanizmalarında önemli rolleri olan siklooksijenaz-2 ve fosfolipaz A2 enzimini arttırdığı diğer çalışmalarda gösterilmiştir (23)(24). Bizim çalışmamızda da benzer şekilde sigara dumanı siklooksijenaz-2, Fosfolipaz A2 ve iNOS enzimlerinin miktarında artışa neden olurken antiinflamatuar özelliği gösterilen alfalinolenik asit bu artışları anlamlı olarak azalttı.…”

Section: Discussionunclassified

Si̇gara Dumaninin Neden Olduğu Akci̇ğer İnflamasyonuna Karşi Alfa-Li̇noleni̇k Asi̇ti̇n Koruyucu Rolü

Kaplan¹,

Doran²

2016

Amaç: Yapılan çalışmalar keten yağında bolca bulunan ve omega 3 yağ asitlerinden biri olan alfa-linolenik asitin antioksidan ve anti inflamatuar etkinliğini göstermiştir. Sigara dumanı birçok zararlı bileşeni içerdiğinden akceğerlerde hasara neden olmaktadır. Bu nedenle alfa-linolenik asitin sigara dumanı maruziyetine bağlı akciğer hasarına karşı koruyucu etkinliği olup olmayacağını planladık.Gereç ve Yöntem: Bu amaçla ferelere 2 ay boyunca sigara dumanı ve 200 mg/kg alfa-linolenik asit verildi. ve akciğerlerindeki siklooksijenaz-2, fosfolipaz A2 ve indüklenebilir nitrik oksit sentaz (iNOS) enzimleri ELISA yöntemiyle analiz edildi. Bulgular:Farelere gentamisin uygulaması akciğerlerde siklooksijenaz-2(COX-2), fosfolipaz A2 ve iNOS enzimlerinin ekpresyonlarını arttırdı. Sigara dumanına maruz bırakılan farelere alfa-linolenik asit verilmesi bu enzimlerdeki artışı geri çevirdi.Sonuç: Çalışmamız sigaranın neden olduğu akciğer hasarına karşı alfa-linolenik asit kullanılmasının yararlı olacağını göstermiştir.