Blocking of protease allergens with inhibitors reduces allergic responses in allergic rhinitis and other allergic diseases.
CONCLUSIONS
Allergic responses specific to the corresponding proteases were reduced by protease inhibitors, suggesting promise as potent treatments for allergic rhinitis and other allergic conditions.


OBJECTIVE
Allergic diseases, such as allergic rhinitis, are caused by the overproduction of IgE antibodies to various allergens. Many reported allergens are proteases that are cysteine, serine, aspartic (acid) proteases and metalloproteases. Conjugation of E64 inhibitor with cysteine protease allergens inhibits the IgE response to the same allergens. However, whether inhibitors of the other protease families reduce IgE levels and whether protease inhibitors reduce allergic symptoms remain controversial. Therefore, we compared the abilities of active and inhibitor-blocked inactive forms of proteases to generate IgE and allergic symptoms in this study to evaluate associations between the allergic response and protease inhibitors.


METHODS
We measured levels of IgE, IgG1, IgG2a, and IgG2b enzyme-specific antibodies, and counted frequency of sneezing and nasal rubbing behavior in mice immunized with active or inactive forms of bromelain, chymotrypsin, chymosin and collagenase (a cysteine protease, a serine protease, an aspartic protease and a metalloprotease, respectively).


RESULTS
All the inhibitors reduced IgE and IgG1 production in response to corresponding enzymes, and a cysteine protease inhibitor, E64, decreased nasal symptoms, such as sneezing and nasal rubbing.
Suzuki
Motohiko
M
Department of Otorhinolaryngology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan. suzumoto@med.nagoya-cu.ac.jp
Itoh
Makoto
M
Ohta
Nobuo
N
Nakamura
Yoshihisa
Y
Moriyama
Akihiko
A
Matsumoto
Tamami
T
Ohashi
Taku
T
Murakami
Shingo
S
D000485:Allergens / Q000276:immunology*; D000818:Animals; D006967:Hypersensitivity / Q000188:drug therapy; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010447:Peptide Hydrolases / Q000276:immunology*; D011480:Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D012221:Rhinitis, Allergic, Perennial / Q000188:drug therapy* / Q000276:immunology
D000485:Allergens; D007074:Immunoglobulin G; D011480:Protease Inhibitors; D007073:Immunoglobulin E; D010447:Peptide Hydrolases