IL-1α antibody inhibits dose-dependent exacerbation of eosinophilic inflammation by crude house-dust-mite antigen in the conjunctiva of an atopic keratoconjunctivitis mouse model
To investigate whether crude house-dust-mite antigen exacerbates eosinophilic inflammation in the conjunctival tissues of an atopic keratoconjunctivitis mouse model in a dose-dependent manner. An atopic keratoconjunctivitis mouse model was established by percutaneous sensitization and crude house-du...
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Published in | Current eye research Vol. 46; no. 8; pp. 1115 - 1124 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
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Taylor & Francis
03.08.2021
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Abstract | To investigate whether crude house-dust-mite antigen exacerbates eosinophilic inflammation in the conjunctival tissues of an atopic keratoconjunctivitis mouse model in a dose-dependent manner.
An atopic keratoconjunctivitis mouse model was established by percutaneous sensitization and crude house-dust-mite antigen application in NC/Nga mice. To assess the dose-dependent response, conjunctival specimens from groups that were administered high- (High-HDM) or low-dose house-dust-mite antigen (Low-HDM) following percutaneous sensitization and the control without house-dust-mite antigen administration (control group) were evaluated. Histological examination and immunofluorescence staining were performed to determine eosinophil density and the number of IL-13-positive cells. Polymerase chain reaction array was used to obtain adaptive and innate immunity-related factor profile, and quantitative polymerase chain reaction was used to determine Il13, Il17a, Ccl11, and Ccl24 expression. Atopic keratoconjunctivitis model mice injected with anti-IL-1α antibody (IL-1α group) or vehicle (vehicle group) to the upper and lower eyelids before atopic keratoconjunctivitis development were evaluated.
Eosinophil density in the conjunctiva increased with house-dust-mite antigen application in a dose-dependent manner. CD4, CXCL10, CCR6, C3, and IL-13 mRNA levels increased more than 5-fold in the conjunctiva of the High-HDM group animals compared to those in control animals. mRNA expression of Il13 and Ccl11 in the conjunctiva of the High-HDM group animals significantly increased compared with that in the Low-HDM and control group animals. Conversely, the eosinophil density and Il13 mRNA expression significantly decreased in the IL-1α group compared with those in the vehicle group.
The house-dust-mite antigen increased eosinophilic infiltration and Il13 mRNA expression in the conjunctiva of an atopic keratoconjunctivitis mouse model in a dose-dependent manner. These inflammatory alterations were partially alleviated by eyelid injection of anti-IL-1α antibody. These findings indicate that IL-1α-induced IL-13 production constitutes a major exacerbating factor for house-dust-mite antigen-induced atopic keratoconjunctivitis. |
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AbstractList | To investigate whether crude house-dust-mite antigen exacerbates eosinophilic inflammation in the conjunctival tissues of an atopic keratoconjunctivitis mouse model in a dose-dependent manner.
An atopic keratoconjunctivitis mouse model was established by percutaneous sensitization and crude house-dust-mite antigen application in NC/Nga mice. To assess the dose-dependent response, conjunctival specimens from groups that were administered high- (High-HDM) or low-dose house-dust-mite antigen (Low-HDM) following percutaneous sensitization and the control without house-dust-mite antigen administration (control group) were evaluated. Histological examination and immunofluorescence staining were performed to determine eosinophil density and the number of IL-13-positive cells. Polymerase chain reaction array was used to obtain adaptive and innate immunity-related factor profile, and quantitative polymerase chain reaction was used to determine Il13, Il17a, Ccl11, and Ccl24 expression. Atopic keratoconjunctivitis model mice injected with anti-IL-1α antibody (IL-1α group) or vehicle (vehicle group) to the upper and lower eyelids before atopic keratoconjunctivitis development were evaluated.
Eosinophil density in the conjunctiva increased with house-dust-mite antigen application in a dose-dependent manner. CD4, CXCL10, CCR6, C3, and IL-13 mRNA levels increased more than 5-fold in the conjunctiva of the High-HDM group animals compared to those in control animals. mRNA expression of Il13 and Ccl11 in the conjunctiva of the High-HDM group animals significantly increased compared with that in the Low-HDM and control group animals. Conversely, the eosinophil density and Il13 mRNA expression significantly decreased in the IL-1α group compared with those in the vehicle group.
The house-dust-mite antigen increased eosinophilic infiltration and Il13 mRNA expression in the conjunctiva of an atopic keratoconjunctivitis mouse model in a dose-dependent manner. These inflammatory alterations were partially alleviated by eyelid injection of anti-IL-1α antibody. These findings indicate that IL-1α-induced IL-13 production constitutes a major exacerbating factor for house-dust-mite antigen-induced atopic keratoconjunctivitis. PURPOSETo investigate whether crude house-dust-mite antigen exacerbates eosinophilic inflammation in the conjunctival tissues of an atopic keratoconjunctivitis mouse model in a dose-dependent manner. MATERIALS AND METHODSAn atopic keratoconjunctivitis mouse model was established by percutaneous sensitization and crude house-dust-mite antigen application in NC/Nga mice. To assess the dose-dependent response, conjunctival specimens from groups that were administered high- (High-HDM) or low-dose house-dust-mite antigen (Low-HDM) following percutaneous sensitization and the control without house-dust-mite antigen administration (control group) were evaluated. Histological examination and immunofluorescence staining were performed to determine eosinophil density and the number of IL-13-positive cells. Polymerase chain reaction array was used to obtain adaptive and innate immunity-related factor profile, and quantitative polymerase chain reaction was used to determine Il13, Il17a, Ccl11, and Ccl24 expression. Atopic keratoconjunctivitis model mice injected with anti-IL-1α antibody (IL-1α group) or vehicle (vehicle group) to the upper and lower eyelids before atopic keratoconjunctivitis development were evaluated. RESULTSEosinophil density in the conjunctiva increased with house-dust-mite antigen application in a dose-dependent manner. CD4, CXCL10, CCR6, C3, and IL-13 mRNA levels increased more than 5-fold in the conjunctiva of the High-HDM group animals compared to those in control animals. mRNA expression of Il13 and Ccl11 in the conjunctiva of the High-HDM group animals significantly increased compared with that in the Low-HDM and control group animals. Conversely, the eosinophil density and Il13 mRNA expression significantly decreased in the IL-1α group compared with those in the vehicle group. CONCLUSIONSThe house-dust-mite antigen increased eosinophilic infiltration and Il13 mRNA expression in the conjunctiva of an atopic keratoconjunctivitis mouse model in a dose-dependent manner. These inflammatory alterations were partially alleviated by eyelid injection of anti-IL-1α antibody. These findings indicate that IL-1α-induced IL-13 production constitutes a major exacerbating factor for house-dust-mite antigen-induced atopic keratoconjunctivitis. |
Author | Yamagami, Satoru Shoji, Jun Shiraki, Yukiko Inada, Noriko Tomioka, Akiko |
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SubjectTerms | Animals Antibodies - therapeutic use Antigens - adverse effects Atopic keratoconjunctivitis Chemokines - genetics Chemokines - metabolism Conjunctiva - immunology Conjunctivitis, Allergic - chemically induced Conjunctivitis, Allergic - genetics Conjunctivitis, Allergic - immunology Conjunctivitis, Allergic - therapy Dermatophagoides farinae - immunology Disease Models, Animal Dose-Response Relationship, Drug eosinophil Eosinophils - immunology Female Fluorescent Antibody Technique, Indirect house-dust-mite IL-13 Inflammation - chemically induced Inflammation - genetics Inflammation - immunology Inflammation - therapy Interleukin-1alpha - immunology Mice mouse model Real-Time Polymerase Chain Reaction RNA, Messenger - genetics Specific Pathogen-Free Organisms |
Title | IL-1α antibody inhibits dose-dependent exacerbation of eosinophilic inflammation by crude house-dust-mite antigen in the conjunctiva of an atopic keratoconjunctivitis mouse model |
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