title: Expression of proteinase-activated receptor (PAR)-2 in monocytes from allergic patients and potential molecular mechanism.
abstract: Serine proteases play an important role in inflammation via PARs. However, little is known of expression levels of PARs on monocytes of allergic patients, and influence of serine proteases and PARs on TNF-α secretion from monocytes. Using quantitative real-time PCR (qPCR) and flowcytometry techniques, we observed that the expression level of PAR-2 in monocytes of patients with allergic rhinitis and asthma was increased by 42.9 and 38.2 %. It was found that trypsin, thrombin, and tryptase induced up to 200, 320, and 310 % increase in TNF-α release from monocytes at 16 h, respectively. PAR-1 agonist peptide, SFLLR-NH2, and PAR-2 agonist peptide tc-LIGRLO-NH2provoked up to 210 and 240 % increase in release of TNF-α. Since SCH 79797, a PAR-1 antagonist, and PD98059, an inhibitor of ERK inhibited thrombin- and SFLLR-NH2-induced TNF-α release, the action of thrombin is most likely through a PAR-1- and ERK-mediated signaling mechanism. Similarly, because FSLLRN-NH2, an inhibitor of PAR-2 diminished tryptase- and tc-LIGRLO-NH2-induced TNF-α release, the action of tryptase appears PAR-2 dependent. Moreover, in vivo study showed that both recombinant cockroach major allergens Per a 1 and Per a 7 provoked upregulation of PAR-2 and PAR-1 expression on CD14+ cells in OVA-sensitized mouse peritoneum. In conclusion, increased expression of PAR-2 in monocytes of AR and asthma implicates that PAR-2 likely play a role in allergy. PAR-2- and PAR-1-mediated TNF-α release from monocytes suggests that these unique protease receptors are involved in the pathogenesis of inflammation.
authors.affiliation: Allergy and Clinical Immunology Research Centre, the First Affiliated Hospital of Liaoning Medical University, No. 2, Section 5, Renmin Street, Guta District, Jinzhou, Liaoning, 121001, People's Republic of China.|Department of Dentistry, the First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning, 121001, China.
authors.forename: Shuqing
authors.initials: S
authors.lastname: Ge
authors.affiliation: Department of Infectious Diseases, Shantou University Medical College, Shantou, 515031, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Infectious Diseases, Shantou University Medical College, Shantou, 515031, China.
authors.forename: Qijian
authors.initials: Q
authors.lastname: Yao
authors.affiliation: Clinical Research Centre, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
authors.forename: Hongling
authors.initials: H
authors.lastname: Yan
authors.affiliation: Allergy and Clinical Immunology Research Centre, the First Affiliated Hospital of Liaoning Medical University, No. 2, Section 5, Renmin Street, Guta District, Jinzhou, Liaoning, 121001, People's Republic of China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Huiyun
authors.affiliation: Department of Infectious Diseases, Shantou University Medical College, Shantou, 515031, China.
authors.forename: Yanshan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Dentistry, the First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning, 121001, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Allergy and Clinical Immunology Research Centre, the First Affiliated Hospital of Liaoning Medical University, No. 2, Section 5, Renmin Street, Guta District, Jinzhou, Liaoning, 121001, People's Republic of China. shoahenghe@hotmail.com.
authors.forename: Shaoheng
authors.initials: S
authors.lastname: He
mesh_terms: D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003058:Cockroaches; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000378:metabolism* / Q000473:pathology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D008954:Models, Biological; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D010533:Peritoneal Lavage; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000378:metabolism*; D012220:Rhinitis / Q000378:metabolism / Q000473:pathology; D013917:Thrombin / Q000494:pharmacology; D014357:Trypsin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D000485:Allergens; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; D044464:Receptor, PAR-2; D014409:Tumor Necrosis Factor-alpha; D048049:Extracellular Signal-Regulated MAP Kinases; D014357:Trypsin; D013917:Thrombin
keywords: Monocyte; Protease-activated receptor; Thrombin; Trypsin; Tryptase; Tumor necrosis factor-α