Tim-3 mRNA expression in peripheral blood lymphocytes from asthmatic patients

Abstract

The study aimed to detect the expression of the Th1-specific cell surface protein T cell Ig and mucin domain-containing molecule-3 (Tim-3) mRNA in peripheral blood lymphocytes isolated from asthmatic patients and to examine the correlation among Tim-3 mRNA, interleukin-4 (IL-4), interferon-γ (IFN-γ) level, and FEV1/FVC (force expiratory volume in one second/forced vital capacity) to explore the role of Tim-3 in the development and progression of asthmatic inflammation. Tim-3 mRNA expression was detected by reverse transcription polymerase chain reaction (RT-PCR). The IL-4 and IFN-γ levels were determined by using enzyme-linked immunosorbent assay (ELISA). The correlation among Tim-3 mRNA, IL-4, IFN-γ level, and pulmonary ventilatory capacity was analyzed. The expression of Tim-3 mRNA in patients with acute asthma exacerbation was 0.39±0.06, significantly higher than that in patients at the remission stage and controls (0.18±0.05 and 0.07±0.03, P<0.05). The level of IL-4 in patients with acute asthma exacerbation was 68.42±10.54, significantly higher than that in the patients at the remission stage and controls (41.83±9.37 and 32.75±8.16, P<0.05). The level of IL-4 in patients in remission was significantly higher than that in controls (P<0.05). The level of IFN-γ in patients with acute asthma exacerbation was 65.74±7.85, significantly lower than that in patients in remission and the control group (120.84±11.62 and 139.65±13.47, P<0.05). The level of IFN-γ in patients in asthma remission was significantly lower than that in controls (P<0.05). Tim-3 mRNA expression was positively correlated with the level of IL-4 (r=0.68, P<0.05) and negatively with the level of IFN-γ and pulmonary ventilatory capacity (r=-0.85, r=-0.76, both P<0.01). The increased expression of Tim-3 mRNA in peripheral blood lymphocytes might be involved in the development and progression of asthmatic inflammation.

Keywords

asthma / airway inflammation / peripheral blood lymphocyte / Tim-3

References

[1] RifkinI R,Marshak-RothsteinA. T-bet: The Toll-bridge to classwitch recombination? Nat Immunol, 2003, 4(4): 650-652

[2] WoodruffP G,FahyJ V. Asthma: prevalence, pathogenesis, and prospects for novel therapies. JAMA, 2001, 286(4):395-398

[3] MonneyL,SabatosC A,GagliaJ L,RyuA,WaldnerH,ChernovaT,ManningS,GreenfieldE A,CoyleA J,SobelR A,FreemanG J,KuchrooV K. Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease. Nature, 2002, 415(6871): 536-541

[4] FukushimaA,SumiT,FukudaK,KumagaiN,NishidaT,AkibaH,OkumuraK,YagitaH, UenoH.Antibodies to T-cell Ig and mucin domain-containing proteins (Tim)-1 and -3 suppress the induction and progression of murine allergic conjunctivitis. Biochem Biophys Res Commun, 2007,353(1):211-216

[5] Asthma Section of Respiratory Disease, Chinese Medical Association. The guide for asthma prevention and cure. Chin J Tuberc Respir Dis, 2003, 26(3): 132-138 (in Chinese)

[6] LittleF F,LynchE,FineG,CenterD M,CruikshankW W. Tumor necrosis factor-alpha-induced synthesis of interleukin-16 in airway epithelial cells: priming for serotonin stimulation. Am J Respir Cell Mol Biol, 2003, 28(3):354-362

[7] PaulW E,SederR A.Lymphocytes responses and cytokines. Cell, 1994, 76(2):241-251

[8] LackG,RenzH,SalogaJ,BradleyK L,LoaderJ,LeungD Y,LarsenG,GelfandE W. Nebulized but not parenteral IFN-g decreases IgE production and normalizes airways functionin a murine modle of allergen sensitization. J Immunol, 1994, 152(5): 2546-2554

[9] NicholsonL B,GreerJ M,SobelR A,LeesM B,KuchrooV K.An altered peptideligand mediates immune deviation and prevents autoimmune en-cephalomyelitis. Immunity, 1995, 3(4): 397-405

[10] KoguchiK,AndersonD E,YangL,O'ConnorK C,KuchrooV K,HaflerD A.Dysregulated T cell expression of Tim3 in multiple sclerosis. J Exp Med, 2006, 203(6): 1413-1418

[11] McIntireJ J,UmetsuS E,AkbariO,PotterM,KuchrooV K,BarshG S,FreemanG J, UmetsuD T,DeKruyffR H.Identification of Tapr (an airway hyperactivity regulatory locus) and the linked Tim gene family. Nat Immunol, 2001, 2(12): 1109-1116

[12] MariatC,Sánchez-FueyoA,AlexopoulosS P,KennyJ,StromT B,ZhengX X.Regulation of T cell dependent immune responses by TIM family members. Philos Trans R Soc Lond B Biol Sci, 2005, 60(1461):1681-1685

[13] SuiL,ZhangW,ChenY,ZhengY,WanT,ZhangW,YangY,FangG,MaoJ,CaoX.Human membrane protein Tim-3 facilitates hepatitis A virus entry into target cells. Int J Mol Med, 2006, 17(6): 1093-1099

RIGHTS & PERMISSIONS

Higher Education Press and Springer-Verlag Berlin Heidelberg