Decreased T-bet expression and changes in chemokine levels in adults with asthma.
T-bet is a novel transcription factor regulating lineage commitment of T helper (Th) lymphocytes to a predominant Th1 phenotype. Previous studies on T-bet and asthma focused mainly on bronchial biopsy specimens. This study assessed the relationship between T-bet expression and levels of selected chemokines in the peripheral blood of asthmatics. Blood was collected from 24 steroid-naive asthmatics, 39 asthmatics on inhaled corticosteroid and 32 age- and sex-matched controls for assay of T-bet expression, specific IgE and chemokines (interferon-gamma inducible protein-10 (IP-10/CXCL10), monokines induced by interferon-gamma (MIG/CXCL9), monocyte chemotactic protein-1 (MCP-1/CCL2), regulated upon activation normal T cell expressed and secreted (RANTES/CCL5) and interleukin-8 (IL-8/CXCL8) levels. T-bet mRNA expression was assessed by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). Chemokine levels were assessed by immunofluorescence flow cytometry. The mean (s.d.) age and forced expiratory volume in 1 s (FEV(1))% predicted of the asthmatics were 43 x 6 (14 x 6) years and 85 x 9 (20.0)%, respectively. The median (IQR) T-bet expression after normalization with beta-actin was suppressed in asthmatics versus controls [asthmatics 0 x 71 (0 x 59) versus controls 1 x 07 (1 x 14), P=0 x 03].The median (IQR) of plasma RANTES was elevated, whereas IP-10 was suppressed in asthmatics versus controls (RANTES: 13658 x 0 (13673 x 3) versus 6299 x 5 (19407 x 8) pg/ml, P=0 x 03; IP-10: 1047 x 6 (589 x 8) versus 1306 x 4 (759 x 9) pg/ml, P=0 x 001). There was a weak and negative correlation between T-bet expression and RANTES level in the asthmatics (r=-0 x 29, P=0 x 032). T-bet could be measured in peripheral blood and its expression was suppressed in asthmatics. This is in keeping with asthma being a predominantly Th2 disease and T-bet probably plays a role in the pathogenesis of asthma. Further studies are needed to explore the potential application of peripheral blood monitoring of T-bet.
Ko
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FW
Department of Medicine and Therapeutics, The Chinese University of Hong Kong. fannyko@cuhk.edu.hk
Lun
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Wong
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CK
Szeto
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CC
Lam
C W K
CW
Leung
T F
TF
Hui
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DS
D000328:Adult; D001249:Asthma / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D016022:Case-Control Studies; D018946:Chemokine CCL5 / Q000097:blood; D054357:Chemokine CXCL10; D018925:Chemokines / Q000097:blood*; D019743:Chemokines, CXC / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D005541:Forced Expiratory Volume; D015870:Gene Expression; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D020825:T-Box Domain Proteins / Q000096:biosynthesis* / Q000235:genetics; D000098815:T-bet Transcription Factor
C114753:CXCL10 protein, human; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D018925:Chemokines; D019743:Chemokines, CXC; D005938:Glucocorticoids; D012333:RNA, Messenger; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor