title: Cell-penetrating peptide derived from human eosinophil cationic protein inhibits mite allergen Der p 2 induced inflammasome activation.
abstract: Newly discovered cell penetration peptides derived from human eosinophil cationic proteins (CPPecp) have the characteristic of cell internalization, but the effect of CPPecp on immunomodulation has not been clarified. House dust mite (HDM) major allergen, Der p 2, can induce proinflammatory cytokine production which contributes to airway inflammation and allergic asthma. However, the mechanism of Der p 2 on NLRP3 inflammasome activation remains unclear. The aim of this study was to investigate the immunomodulatory effect of CPPecp on inhibition of Der p 2 induced inflammasome activation. We showed that proinflammatory cytokines IL-1β, IL-6 and IL-8 were significantly upregulated in peripheral blood mononuclear cells (PBMCs) derived from HDM allergic patients after Der p 2 stimulation. Expression of NLRP3, ASC, Caspase-1, IL-1β and Caspase-1 activity was upregulated in THP-1 cells after Der p 2 stimulation. Proinflammatory cytokine production, NLRP3 inflammasome activation and caspase-1 activity were downregulated in THP-1 cells and CD14+ cells co-cultured with Der p 2 and CPPecp. The immunomodulatory effect of CPPecp was through upregulation of IFN-α production but not induction of autophagy. These results suggested Der p 2 plays an important role in NLRP3 inflammasome activation and CPPecp has the potential to be a novel anti-inflammatory agent for allergic inflammation treatment in the future.
authors: Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan; Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
authors: Sheng-Jie
authors: SJ
authors: Yu
authors: Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan; Department of BioIndustry Technology, Da Yeh University, Changhua, Taiwan; Department of Medical Technology, Jen Ten College of Medicine, Nursing and Management, Miaoli, Taiwan.
authors: En-Chih
authors: EC
authors: Liao
authors: Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan; Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
authors: Meei-Ling
authors: ML
authors: Sheu
authors: Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan.
authors: Dah-Tsyr Margaret
authors: DT
authors: Chang
authors: Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan; Section of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan.
authors: Jaw-Ji
authors: JJ
authors: Tsai
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology / Q000378:metabolism*; D060829:Arthropod Proteins / Q000276:immunology / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D020170:Caspase 1 / Q000276:immunology / Q000378:metabolism; D057846:Cell-Penetrating Peptides / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D058847:Inflammasomes / Q000276:immunology / Q000378:metabolism*; D016898:Interferon-alpha / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D016209:Interleukin-8 / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D039981:Pyroglyphidae / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; C451163:Dermatophagoides pteronyssinus antigen p 2; D058847:Inflammasomes; D016898:Interferon-alpha; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D020170:Caspase 1