House dust mite allergen Der f 1 can induce the activation of latent TGF-beta via its protease activity.
A major house dust mite allergen Der f 1 belongs to the papain-like cysteine protease family. This study investigated whether Der f 1 can cleave the latency-associated peptide (LAP) of transforming growth factor (TGF)-beta via its proteolytic activity and activate latent TGF-beta. We found that Der f 1 can cleave LAP and induce the activation of latent TGF-beta, leading to functional Smad signaling. Importantly, these actions of Der f 1 were inhibited by cysteine protease inhibitor E64 or inactivation of the protease activity by heat. Thus, latent TGF-beta may be a direct target of Der f 1 protease activity.
Nakamura
Yuki
Y
Department of Immunology, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.
Miyata
Masanori
M
Shimokawa
Naomi
N
Ohnuma
Yuko
Y
Katoh
Ryohei
R
Ogawa
Hideoki
H
Okumura
Ko
K
Nakao
Atsuhito
A
D000485:Allergens / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000008:administration & dosage / Q000187:drug effects / Q000378:metabolism*; D060829:Arthropod Proteins; D003546:Cysteine Endopeptidases / Q000276:immunology / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D015870:Gene Expression; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D039981:Pyroglyphidae / Q000201:enzymology / Q000276:immunology; D015398:Signal Transduction; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D000485:Allergens; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D015853:Cysteine Proteinase Inhibitors; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D003546:Cysteine Endopeptidases; C451159:Dermatophagoides farinae antigen f 1; D007930:Leucine; C024974:E 64