Exposure in vivo to silica or lipopolysaccharide produces transient or sustained upregulation, respectively, of PYPAF7 and MEFV genes in bronchoalveolar lavage cells in rats.
A family of proteins containing PAAD [for PYRIN, AIM (absent in melanoma), apoptosis-associated protein speck-like protein containing a caspase recruitment domain, and death domain] domain was found to be involved in modulating inflammatory responses, by its ability to regulate nuclear factor (NF)-kappaB and procaspase-1 activation. In this study, intratracheal instillation of silica in rats was found to produce transient upregulation of mRNA levels of the PAAD family of proteins, PYPAF7 (PYRIN containing Apaf1-like protein; Apaf stands for apoptosis activating factor) and MEFV (for Mediterranean fever), in bronchoalveolar lavage (BAL) cells. The levels were markedly elevated at 4 h, returning to basal levels by 24 h. In contrast, intratracheal instillation of LPS produced a sustained upregulation of the two genes in BAL cells. In vitro exposure of BAL cells to silica or lipopolysaccharide (LPS) produced no changes in the expression of these genes, indicating that silica or LPS exposure in vivo induces some factors that are responsible for the upregulation of PYPAF7 and MEFV. The mRNA levels of these two genes in peripheral blood monocytes and PMN following LPS exposure did not change, indicating that AM and peripheral blood cells show similar response to LPS exposure in vitro. This study provides the basis for a physiological model to study the effects of these two genes in modulating the inflammatory response after particle exposure.
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, USA. mir8@cdc.gov
K Murali Krishna
KM
Rao
Terence
T
Meighan
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis* / Q000502:physiology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003598:Cytoskeletal Proteins / Q000096:biosynthesis*; D020869:Gene Expression Profiling; D007249:Inflammation; D008070:Lipopolysaccharides / Q000633:toxicity*; D009000:Monocytes; D010316:Particle Size; D000071198:Pyrin; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide / Q000633:toxicity*; D015854:Up-Regulation
D051017:Apoptosis Regulatory Proteins; D003598:Cytoskeletal Proteins; D008070:Lipopolysaccharides; D000071198:Pyrin; D012333:RNA, Messenger; D012822:Silicon Dioxide