Mob-1 expression in IL-2-induced ARDS: regulation by TNF-alpha.
We have recently established an animal model of adult respiratory distress syndrome (ARDS)-like microvascular lung injury elicited by infusion of human interleukin-2 (IL-2). Based on the pronounced, transcriptional upregulation of multiple pro-inflammatory mediators in IL-2-induced ARDS, differential display was applied to search for potentially novel genes in this paradigm of lung injury. Differential display on total lung RNA derived from IL-2-challenged rats presented a highly reproducible 3'-UTR fragment profile in which a band (approximately 250 bp), termed B1, was strongly induced. B1 cDNA sequence exhibited 99.14% homology to the 3'-UTR of mob-1, a recently cloned gene belonging to the C-X-C chemokine superfamily. Furthermore, Northern blot analysis showed that IL-2-induced pulmonary mob-1 mRNA was expressed at time points before the onset of lung injury and suppressed after TNF-alpha inhibition. These data imply that lung mob-1 is a novel, highly inducible gene in a clinically relevant model of ARDS and, based on its identification as a chemokine, could participate in the development of lung injury.
Neville
L F
LF
Department of Surgery, Jefferson Medical College, Philadelphia 19107, USA.
Abdullah
F
F
McDonnell
P M
PM
Young
P R
PR
Feuerstein
G Z
GZ
Rabinovici
R
R
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D006224:Cricetinae; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins; D012128:Respiratory Distress Syndrome / Q000139:chemically induced* / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; C091326:Cxcl10 protein, rat; D016207:Cytokines; D007376:Interleukin-2; D015335:Molecular Probes; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha