This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall focus of the SCOR program is sepsis-induced acute lung injury. The SCOR program does not try to address all of the basic and clinical issues related to sepsis-induced acute lung injury. Specific focus and rationale for the SCOR program is as follows: During gram-sepsis, endotoxin and bactrial DNA are released and stimulate macrophages to release TNF. Cell wall products of gram positive organisms mimic the effects of endotoxin on macrophages. TNF can trigger organ and cellular dysfunction (decreased surfactant production) and/or injury (by apoptosis). Projects 1 and 2 evaluate the regulation of cytokine genes (including TNF) in human alveolar macrophages (Project 1) and liver (Project 2). Project 1 evaluates the role of MAPK's and Project 2 evaluates redox regulation of NFkB. The Clinical Core will provide human tissues and biometry support for the two projects.