Impact of female cigarette smoking on circulating B cells in vivo: the suppressed ICOSLG, TCF3, and VCAM1 gene functional network may inhibit normal cell function.
As pivotal immune guardians, B cells were found to be directly associated with the onset and development of many smoking-induced diseases. However, the in vivo molecular response of B cells underlying the female cigarette smoking remains unknown. Using the genome-wide Affymetrix HG-133A GeneChip microarray, we firstly compared the gene expression profiles of peripheral circulating B cells between 39 smoking and 40 non-smoking healthy US white women. A total of 125 differential expressed genes were identified in our study, and 75.2% of them were down-regulated in smokers. We further obtained genotypes of 702 single nucleotide polymorphisms in those promising genes and assessed their associations with smoking status. Using a novel multicriteria evaluation model integrating information from microarray and the association studies, several genes were further revealed to play important roles in the response of smoking, including ICOSLG (CD275, inducible T-cell co-stimulator ligand), TCF3 (E2A immunoglobulin enhancer binding factors E12/E47), VCAM1 (CD106, vascular cell adhesion molecule 1), CCR1 (CD191, chemokine C-C motif receptor 1) and IL13 (interleukin 13). The differential expression of ICOSLG (p = 0.0130) and TCF3 (p = 0.0125) genes between the two groups were confirmed by real-time reverse transcription PCR experiment. Our findings support the functional importance of the identified genes in response to the smoking stimulus. This is the first in vivo genome-wide expression study on B cells at today's context of high prevalence rate of smoking for women. Our results highlight the potential usage of integrated analyses for unveiling the novel pathogenesis mechanism and emphasized the significance of B cells in the etiology of smoking-induced disease.
Pan
Feng
F
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, People's Republic of China.
Yang
Tie-Lin
TL
Chen
Xiang-Ding
XD
Chen
Yuan
Y
Gao
Ge
G
Liu
Yao-Zhong
YZ
Pei
Yu-Fang
YF
Sha
Bao-Yong
BY
Jiang
Yan
Y
Xu
Chao
C
Recker
Robert R
RR
Deng
Hong-Wen
HW
D000328:Adult; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D060945:Inducible T-Cell Co-Stimulator Ligand; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012907:Smoking / Q000235:genetics* / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism
D015703:Antigens, CD; D051792:Basic Helix-Loop-Helix Proteins; D060945:Inducible T-Cell Co-Stimulator Ligand; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; C498514:ICOSLG protein, human; C407909:TCF3 protein, human