Chemokine synthesis and cellular inflammatory changes in lungs of mice bearing p40tax of human T-lymphotropic virus type 1.
To elucidate the pathogenic mechanisms of human T-lymphotropic virus type 1 (HTLV-1)-associated lung inflammation, we conducted a histopathological and molecular analysis study using transgenic mice bearing pX region of this virus. In these mice, accumulations of inflammatory cells consisting mainly of lymphocytes were present in peribronchiolar and perivascular areas and alveolar septa, while control littermate mice did not show such changes. In situ hybridization showed that the anatomic distribution of p40tax mRNA was similar to that of inflammatory cells, typically in peribronchiolar areas and to a lesser extent in perivascular and alveolar septa. Inflammatory cytokines, including IL-1beta, tumour necrosis factor-alpha and interferon-gamma, and several chemokines, such as monocyte chemotactic protein-1 (MCP-1), RANTES, macrophage inflammatory protein-1alpha (MIP-1alpha) and IP-10, were detected in lungs of transgenic mice but not control mice. Semiquantitative analysis using reverse transcription-polymerase chain reaction showed a significant correlation between MCP-1 mRNA expression and p40tax mRNA, but not with other chemokines. The gene expression of the above chemokines, with the exception of MIP-1alpha, correlated with the severity of histopathological changes in the lung. Considered together, our results suggested that p40tax synthesis may be involved in the development of lung lesions caused by HTLV-1 through the induction of local production of chemokines.
Miyazato
A
A
First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
Kawakami
K
K
Iwakura
Y
Y
Saito
A
A
D000818:Animals; D018925:Chemokines / Q000096:biosynthesis*; D016356:Gene Products, tax / Q000096:biosynthesis* / Q000235:genetics; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D008171:Lung Diseases / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000378:metabolism
D018925:Chemokines; D016356:Gene Products, tax; D012333:RNA, Messenger