German Cockroach Frass Proteases Modulate the Innate Immune Response via Activation of Protease-Activated Receptor-2

Day, Scottie B.; Zhou, Ping; Ledford, John R.; Page, Kristen

doi:10.1159/000317195

Cited by 29 publications

(33 citation statements)

References 64 publications

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“…and Clostridium difficile) (Hansen et al, 2005;Cottrell et al, 2007), and allergen-derived proteases (cockroaches and dust mites) (Shpacovitch et al, 2008;Day et al, 2010). Although concentrations of PAR2-activating serine proteases (i.e., trypsin and ␤-tryptase) increase in colonic luminal fluid in human and animal IBDs Hansen et al, 2005;Kawabata et al, 2008;Lee et al, 2010), recent evidence suggests that pathogenic PAR2-activating proteases may come from within the colon wall itself (Lau et al, 2010) and not the lumen (Barbara and Cremon, 2008).…”

Section: Downloaded Frommentioning

confidence: 99%

Antagonism of Protease-Activated Receptor 2 Protects against Experimental Colitis

Lohman

Cotterell²,

Suen³

et al. 2011

J Pharmacol Exp Ther

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Many trypsin-like serine proteases such as ␤-tryptase are involved in the pathogenesis of colitis and inflammatory bowel diseases. Inhibitors of individual proteases show limited efficacy in treating such conditions, but also probably disrupt digestive and defensive functions of proteases. Here, we investigate whether masking their common target, protease-activated receptor 2 (PAR2), is an effective therapeutic strategy for treating acute and chronic experimental colitis in rats. A novel PAR2 antagonist (5-isoxazoyl-Cha-Ile-spiro[indene-1,4Ј-piperidine]; GB88) was evaluated for the blockade of intracellular calcium release in colonocytes and anti-inflammatory activity in acute (PAR2 agonist-induced) versus chronic [2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced] models of colitis in Wistar rats. Disease progression (disease activity index, weight loss, and mortality) and postmortem colonic histopathology (inflammation, bowel wall thickness, and myeloperoxidase) were measured. PAR2 and tryptase colocalization were investigated by using immunohistochemistry. GB88 was a more potent antagonist of PAR2 activation in colonocytes than another reported compound, N 1 -3-methylbutyryl-N 4 -6-aminohexanoyl-piperazine (ENMD-1068) (IC 50 8 M versus 5 mM). Acute colonic inflammation induced in rats by the PAR2 agonist SLIGRL-NH 2 was inhibited by oral administration of GB88 (10 mg/kg) with markedly reduced edema, mucin depletion, PAR2 receptor internalization, and mastocytosis. Chronic TNBS-induced colitis in rats was ameliorated by GB88 (10 mg/kg/day p.o.), which reduced mortality and pathology (including colon obstruction, ulceration, wall thickness, and myeloperoxidase release) more effectively than the clinically used drug sulfasalazine (100 mg/ kg/day p.o.). These disease-modifying properties for the PAR2 antagonist in both acute and chronic experimental colitis strongly support a pathogenic role for PAR2 and PAR2-activating proteases and therapeutic potential for PAR2 antagonism in inflammatory diseases of the colon.

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confidence: 99%

Antagonism of Protease-Activated Receptor 2 Protects against Experimental Colitis

Lohman

Cotterell²,

Suen³

et al. 2011

J Pharmacol Exp Ther

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“…GC frass is complex and contains a number of early innate immune response activators, including endotoxin, a Toll-like receptor (TLR) 4 agonist, a TLR2 agonist [6] and active serine proteases which activate protease-activated receptor-2 [7] . However, the early events that facilitate the development of the pathogenic Th2 response following initial exposure to GC frass are currently unclear.…”

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confidence: 99%

Early Immunological Response to German Cockroach Frass Exposure Induces a Th2/Th17 Environment

Page¹,

Zhou²,

Ledford³

et al. 2010

J Innate Immun

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Cockroach exposure is a major risk factor for the development of asthma; however, the early immune events induced by cockroach leading to the Th2 response are not fully understood. Exposure of naïve mice to German cockroach (GC) feces (frass) was sufficient to induce dendritic cell (DC) recruiting and activating chemokines C-C motif ligand 20, granulocyte macrophage colony-stimulating factor, granulocyte colony-stimulating factor and macrophage inflammatory protein-1α into the airways. This corresponded with an increase in myeloid DCs (mDCs) in the airways as well as increased expression of CD80 and CD86 on the mDCs. Plasmacytoid DCs in the lung were unchanged. Levels of IL-5, IL-17A and IL-6 cytokines in whole lung cultures were significantly increased 18 h following GC frass exposure demonstrating the early development of a mixed Th2/Th17 response. In addition, GC frass stimulated the production of IL-23, IL-6 and IL-12p70 from bone marrow-derived mDCs. Adoptive transfer of GC frass-pulsed mDCs induced airway reactivity, airway inflammation as well as eosinophilia and induced a strong Th2/Th17 response in the lung. MyD88-deficient bone marrow-derived mDCs did not respond to GC frass treatment, suggesting a functional Toll-like receptor pathway was important to induce the Th2/Th17 response. Together, our data show that GC frass activated the innate immune response to augment DC recruitment and activation of mDCs which promoted robust T cell-skewing cytokines and ultimately drive the development of airway inflammation.

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“…Bla g 1 allerjeninin Th2 sitokin üretimine yol açtığı gösterilmiştir. Yine Per a 3'ün T hücre proliferasyonuna yol açtığı bilinmektedir (19).…”

Section: Hamamböceği Allerjeni -İmmün Hücre (Dendritik Ve T Hücre) Etunclassified

Cockroach Allergy and Its Immunotherapy

Özdemir

Aydın

2016

Asthma Allergy Immunol

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ÖZHamamböceği allerjisi 30 yılı aşkın süredir, solunum yolu allerjik hastalıklarının önemli bir nedeni olarak düşünülmektedir. En sık evcil hamamböceği türleri Alman (Blattella germanica) ve Amerikan (Periplaneta americana) hamamböcekleridir. Alman hamamböceği küçük, 16 mm boyunda, tüm dünyada evlerde bulunan bir böcektir. Amerikan hamamböceği daha büyük, 35-53 mm boyutunda, ev, hastane, okul ve diğer büyük binalarda da bulunabilen bir böcektir. Türkiye' de 20' den fazla hamamböceği türü olmasına rağmen, en sık Alman hamamböceğine rastlanır. ABD' de çocuk ve erişkinleri içeren değişik araştırmalarda hamamböceği allerjisi %17-41 arasında bulunmuştur. Avrupa' da allerji kliniğine başvuran çocuk ve erişkinlerde yapılan çalışmalarda ise, %4-26 oranında saptanmıştır. Türkiye' de hamamböceği allerjisi prevalansı çocuk ve erişkinleri içeren değişik araştırmalarda %2.2-51.4 arasında bildirilmiştir. Tropomyosin, Bla g7 ve Per a7 denilen, hamamböceklerindeki major allerjenlerden biridir. Ayrıca tropomyosin, böceklerle omurgasızlar (akar, kabuklular, yumuşakca ve parazitler) arasındaki çapraz reaktivitede rol oynayan bir allerjendir. Hamamböceğine duyarlı kişilerde, diğer omurgasızların allerjenlerine kosensitizasyon yaygın bir özelliktir. Böylece, parazit enfestasyonları çapraz reaktif antikorlar aracılığıyla allerjik reaktiviteyi regüle ederler. Hamamböceği allerjen düzeyini tamamen başarılı bir temizlikten sonrası bile sürekli düşük tutmak zor olmasına ilaveten, hamamböceği allerjisinin teşhis ve tedavisinde kullanılan ticari ekstraktlar standardize değildirler. Bazı çalışmalar hamamböceğine karşı immünoterapinin etkili olduğunu düşündürmesine rağmen; kaliteli ekstraktlar, daha çok sayıda ve daha uzun süre takip edilen hastalar ile yapılacak randomize kontrollü çalışmalar bu tedavinin etkinlik ve güvenilirliğini göstermek için gereklidir. ABSTRACTCockroach allergy has been considered as an important cause of respiratory allergic diseases for over three decades. The most common domiciliary cockroach species are Blattella germanica (German cockroach) and Periplaneta americana (American cockroach). Blattella germanica is a small cockroach, approximately 16 mm in length, which commonly infests houses worldwide. Periplaneta americana is a large cockroach, approximately 35-53 mm in length, that infests houses, schools, hospitals, and other large buildings. There are more than 20 different cockroach species in Turkey, and Blattella germanica is known as the most common. In the United States, the prevalence of cockroach allergy ranges from 17 to 41%'in various studies involving both children and adults. European studies on children and adults attending an allergy clinic show a high variability in cockroach sensitisation varying from %4-26. In Turkey, cockroach allergy prevalence rate varies from %2.2-51.4 in different studies consisting of both children and adults. Tropomyosin, designated as Bla g7 and Per a7, has been identified as a major allergen in cockroaches. Tropomyosin is also an important allergen involved in cross-rea...

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German Cockroach Frass Proteases Modulate the Innate Immune Response via Activation of Protease-Activated Receptor-2

Cited by 29 publications

References 64 publications

Antagonism of Protease-Activated Receptor 2 Protects against Experimental Colitis

Antagonism of Protease-Activated Receptor 2 Protects against Experimental Colitis

Early Immunological Response to German Cockroach Frass Exposure Induces a Th2/Th17 Environment

Cockroach Allergy and Its Immunotherapy

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