title: In Vitro Pro-inflammatory Regulatory role of Substance P in Alveolar Macrophages and Type II Pneumocytes after JP-8 Exposure.
abstract: The effects of JP-8 on pro-inflammatory cytokine interleukin (IL)-1alpha,beta and nitric oxide (NO) secretion as well as the role of substance P (SP) in these processes were examined in cultured alveolar macrophages (AM), type II epithelial cells (AIIE), and AM/AIIE co-cultures. Exposure of AM to JP-8 for 24 hr exhibited release of IL-1alpha,beta, whereas exposure to AIIE showed a concentration-dependent NO overproduction. Data indicate that there are cell-dependent inflammatory mechanisms responsible for the actual level of JP-8 exposure in alveoli. However, treatment with substance P significantly attenuated JP-8 induced the IL-1alpha,beta secretion. This finding was confirmed by using [Sar(9) Met (O(2))(11)] SP (10(- 10) M), an agonist of substance P, suggesting that substance P may have signal pathway(s) to AM in the inflammatory response mediated by IL-1. Moreover, AM/AIIE co-culture obviously reduced NO overproduction observed in AIIE alone, suggesting that there may be cell interactions or communications between AM and AIIE in response to the JP-8 exposure.
authors.affiliation: Department of Pediatrics and Center for Toxicology, University of Arizona, Tucson, Arizona, USA.
authors.forename: Nina N
authors.initials: NN
authors.lastname: Sun
authors.forename: Simon S
authors.initials: SS
authors.lastname: Wong
authors.forename: Celine
authors.initials: C
authors.lastname: Nardi
authors.forename: Daniel
authors.initials: D
authors.lastname: Ostroff
authors.forename: Mark L
authors.initials: ML
authors.lastname: Witten
authors.forename: R Clark
authors.initials: RC
authors.lastname: Lantz