Inverse association between T-cell immunoglobulin and mucin domain-1 and T-bet in a mouse model of allergic rhinitis.
BACKGROUND
It has been suggested that human hepatitis A virus cellular receptor, also known as T-cell immunoglobulin and mucin domain-1 (TIM-1), plays an important role in the development of allergic diseases on the basis of epidemiologic data, but the molecular mechanism has been unclear. In a murine model of ovalbumin (OVA)-sensitized allergic rhinitis (AR), we examined the expression of TIM-1 and its correlation with T helper1-associated transcription factor, T-bet, as a potential mediator of T-cell immunoglobulin expression.


METHODS
Mice were challenged intranasally with OVA to elicit AR. The expression of TIM-1 in nasal tissues was examined by real-time reverse-transcription polymerase chain reaction (RT-PCR), and the surface expression of TIM-1 in peripheral blood mononuclear cells was evaluated by means of flow cytometry. In addition, the expression of TIM-1 as well as T-bet in splenic lymphocytes was examined by Western blotting.


RESULTS
TIM-1 mRNA was increased significantly in nasal tissues (P < .05) as seen by real-time RT-PCR. Flow cytometry indicated a differential TIM-1 expression of 135.5 +/- 34.2 in the AR group versus 51.1 +/- 10.9 in the control group (P < .05). The mean values of normalized TIM-1 were 0.43 +/- 0.18 and 0.21 +/- 0.10 in AR and control groups, respectively, whereas the mean values of normalized T-bet were 0.22 +/- 0.13 and 0.67 +/- 0.17 in the AR and control groups, respectively. There was a significant difference in the production of TIM-1 as well as T-bet in AR mice versus control mice (P < .05). The increased production of TIM-1 correlated significantly with the decreased T-bet in spleen tissue of AR mice (r = -0.52, P < .05).


CONCLUSIONS
Our experimental model recapitulates an increase in lymphocyte TIM-1 expression seen in AR both locally and systemically. Our results also demonstrate an inverse relationship between lymphocyte TIM-1 and T-bet expression, suggesting a possible mechanism that TIM-1 influences the development of AR.
Xu
Geng
G
Otorhinolaryngology Hospital of The First Affiliated Hospital of Sun Yat-sen University and the Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, China.
Cheng
Lei
L
Wen
Weiping
W
Oh
Yun
Y
Mou
Zhonglin
Z
Shi
Jianbo
J
Xu
Rui
R
Li
Huabin
H
D000818:Animals; D015153:Blotting, Western; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D000072596:Hepatitis A Virus Cellular Receptor 1; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009077:Mucins / Q000235:genetics / Q000276:immunology*; D010047:Ovalbumin / Q000493:pharmacokinetics; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D006255:Rhinitis, Allergic, Seasonal / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology*; D000098815:T-bet Transcription Factor
D017931:DNA Primers; C442240:Havcr1 protein, mouse; D000072596:Hepatitis A Virus Cellular Receptor 1; D008565:Membrane Proteins; D009077:Mucins; D012333:RNA, Messenger; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D010047:Ovalbumin