Antiallergic effects of anti-interleukin-33 are associated with suppression of immunoglobulin light chain and inducible nitric oxide synthase.
OBJECTIVE
We aimed to find novel genes that are significantly induced in allergic mice and that are significantly downregulated with anti-interleukin (IL) 33 treatment.


METHODS
Thirty-six mice were allocated into each of group A (intraperitoneal [i.p.]) sensitized and intranasally challenged to saline solution), group B (sensitized and challenged to ovalbumin), group C (sensitized and challenged with ovalbumin, and null treatment with i.p. saline solution), and group D (sensitized and challenged with ovalbumin, and treatment with anti-IL-33 i.p. injection). We counted the number of nose-scratching in 10 minutes, serum ovalbumin-specific immunoglobulin E (IgE), and titers of cytokines (IL-1, IL-4, IL-5, IL-10, IL-13) in bronchoalveolar lavage fluid. By using one whole lung from each mouse, we performed microarray analysis and real-time polymerase chain reaction.


RESULTS
group D showed a significantly reduced nose-scratching events and lower serum ovalbumin-specific IgE compared with groups B and C. All the cytokines in the bronchoalveolar lavage fluid were significantly decreased after anti-IL-33 treatment. Microarray analysis revealed that group B (immunoglobulin free light chain [IgFLC], 89.1 times; nitric oxide synthase [NOS] 2, 11.5 times) and group C (IgFLC, 141.6 times; NOS2, 11.7 times) had significantly increased expression of IgFLC and NOS2 genes compared with group A. After anti-IL-33 treatment, group D showed significantly decreased expression of both IgFLC (49.3 times) and NOS2 (6.5 times). In real-time polymerase chain reaction, groups B and C had significantly increased expression of these genes (IgFLC, 10.4 times and 29 times, respectively; NOS2, 3.8 times and 4.5 times, respectively). After treatment, group D showed significantly decreased expression of IgFLC (5.0 times) and NOS2 (2.5 times).


CONCLUSIONS
The antiallergic effect of anti-IL-33 can be explained by suppression of IgFLC and NOS2 in a murine model of allergic rhinitis.
Department of Pharmacology, Hypoxia-Related Disease Research Center, Inha Research Institute for Medical Sciences, Inha University College of Medicine, Incheon, Republic of Korea.
Chang-Shin
CS
Park
Tae Young
TY
Jang
Min-Jeong
MJ
Heo
Ah-Yeoun
AY
Jung
Young Hyo
YH
Kim
D000818:Animals; D019138:Antibodies, Blocking / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy*; D007073:Immunoglobulin E / Q000097:blood; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000378:metabolism*; D007167:Immunotherapy / Q000379:methods*; D000067596:Interleukin-33 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D046228:Microarray Analysis; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*
D019138:Antibodies, Blocking; D007147:Immunoglobulin Light Chains; D000067596:Interleukin-33; D007073:Immunoglobulin E; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse