Inverse association between T-cell immunoglobulin and mucin domain-1 and T-bet in a mouse model of allergic rhinitis

Laryngoscope. 2007 Jun;117(6):960-4. doi: 10.1097/mlg.0b013e318041549c.

Abstract

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).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • DNA Primers / genetics
  • Disease Models, Animal
  • Female
  • Flow Cytometry
  • Hepatitis A Virus Cellular Receptor 1
  • Leukocytes, Mononuclear / immunology
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mucins / genetics
  • Mucins / immunology*
  • Ovalbumin / pharmacokinetics
  • Protein Structure, Tertiary / genetics
  • Protein Structure, Tertiary / physiology*
  • RNA, Messenger / genetics
  • RNA, Messenger / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rhinitis, Allergic, Seasonal / genetics
  • Rhinitis, Allergic, Seasonal / immunology*
  • Rhinitis, Allergic, Seasonal / metabolism
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / immunology*

Substances

  • DNA Primers
  • Havcr1 protein, mouse
  • Hepatitis A Virus Cellular Receptor 1
  • Membrane Proteins
  • Mucins
  • RNA, Messenger
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Ovalbumin