High expression of p40(tax) and pro-inflammatory cytokines and chemokines in the lungs of human T-lymphotropic virus type 1-related bronchopulmonary disorders.
OBJECTIVE
Human T-lymphotropic virus type 1 (HTLV-1) is closely associated with the development of certain pulmonary diseases, such as bronchiolitis, although the pathologic mechanism remains unclear. To elucidate the pathogenesis of HTLV-1-associated bronchopulmonary disorders, we analyzed the relationship between expression of p40(tax), a regulatory component of HTLV-1 that stimulates various host genes, and synthesis of pro-inflammatory cytokines and chemokines by cells in BAL fluid (BALF) obtained from HTLV-1-infected patients.


METHODS
Reverse transcription-polymerase chain reaction was used to compare the expression of p40(tax) and pro-inflammatory cytokines and chemokines messenger RNA (mRNA) in BALF of 10 HTLV-1 carriers and 7 healthy subjects. We also studied the correlation between these parameters and the proportion of lymphocytes in BALF.


RESULTS
The expression levels of pro-inflammatory cytokines (interferon [IFN]-gamma, interleukin-2) and chemokines (monocyte chemotactic protein-1, macrophage inflammatory protein [MIP]-1alpha, IFN-gamma-inducible protein-10 [IP-10]) were significantly higher in BALF of patients than of healthy subjects. The expression of IFN-gamma and MIP-1alpha mRNA correlated with that of p40(tax). IFN-gamma and IP-10 mRNA expression correlated with the proportion of lymphocytes in BALF. The percentage of lymphocytes in BALF increased with higher expression levels of p40(tax) mRNA, although the correlation was not significant.


CONCLUSIONS
Our results suggested that p40(tax) seems be involved in the development of HTLV-1-associated bronchopulmonary disorders at least in part through the local production of pro-inflammatory cytokines and chemokines.
Yamazato
Yoriko
Y
First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0125, Japan.
Miyazato
Akiko
A
Kawakami
Kazuyoshi
K
Yara
Satomi
S
Kaneshima
Hiroshi
H
Saito
Atsushi
A
D000328:Adult; D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000821:virology; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D016356:Gene Products, tax / Q000235:genetics* / Q000502:physiology; D015481:HTLV-I Antibodies / Q000302:isolation & purification; D015490:HTLV-I Infections / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D008171:Lung Diseases / Q000209:etiology / Q000378:metabolism / Q000821:virology*; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016207:Cytokines; D016356:Gene Products, tax; D015481:HTLV-I Antibodies; D007376:Interleukin-2; D007371:Interferon-gamma