Pseudomonas aeruginosa induced lung damage is through caspase-1 mediated IL-1β and MIP-2 expression

• Main Authors: Chia-Chi Tsai, 蔡佳琪
• Other Authors: Lee-Wei Chen
• Format: Others
• Language: en_US
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/21266687148690643180

碩士 === 國立中山大學 === 生物科學系研究所 === 100 === Pseudomonas aeruginosa-induced pneumonia is serious problem that results in severe inflammation response and high mortality in the host. Interleukin-1β (IL-1β) is one of the major extracellular proinflammatory cytokines thought to be involved in many acute and chronic lung diseases. To investigate the role of caspase-1, IL-1β and macrophage inflammatory protein-2 (MIP-2) in P. aeruginosa pneumonia induced lung damage, C57BL/6 (WT) and CASP-1-/- mice were subjected to pneumonia induced by intratracheal injection of P. aeruginosa. The lung permeability, bacterial content in blood and lung, lung myeloperoxidase (MPO) activity, total cell counts and protein in bronchoalveolar lavage fluid (BALF), NF-κB activation as well as expression of IL-1β and MIP-2 were assayed at 8 hr after P. aeruginosa injection. The IL-1β inhibitor, anakinra, was also used to evaluate the role of IL-1β. P. aeruginosa injection increased the lung permeability, lung MPO activity, bacterial counts in blood, total cell counts and protein in BALF, NF-κB activation and expression of IL-1β and MIP-2 in WT mice; and these increases were all decreased by administration of anakinra in WT mice or in CASP-1-/- mice. Furthermore, the lung MPO activity, total protein in BALF and expression of IL-1β and MIP-2 were decreased in CASP-1-/- → WT but not in WT → CASP-1-/- chimeric mice, suggesting that pneumonia induced lung damage and IL-1β and MIP-2 expressions depend on caspase-1 signaling of the resident cells.