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The possible contribution of Rho\/Ras signaling pathways was examined by using geranylgeranyl-pyrophosphate (GGPP) and farnesyl-pyrophosphate (FPP), the selective geranylgeranyl-pyrophosphate-transferase inhibitor GGTI2133, and the selective farnesyl-pyrophosphate transferase inhibitor FTI276, the hydroxy-3-methylglutaryl coenzyme A reductase inhibitor simvastatin and the Rho-associated coiled-coil\u2013forming protein serine\/threonine kinase inhibitor Y27632. LPS (300 ng\/ml) significantly enhanced the EFS-induced contractile force of human bronchi (P &amp;lt; 0.05). The plateau was reached at 105.0 (\u00b14.1) minutes; the maximal effect (Emax) value was 267.47 (\u00b18.88) %, with a time to evoke a half-maximal contraction (t1\/2) of 40.5 (\u00b12.0) minutes. Pretreatment with GGPP (5 \u03bcM) enhanced the EFS-mediated contractile tension (Emax, 164.56 \u00b1 9.80% and the t1\/2 23.0 \u00b1 2.5 min). Pretreatment with FPP (5 \u03bcM) was effective, as was GGPP, in enhancing the EFS response (Emax, of 189.23 \u00b1 12.98% and a t1\/2 of 17.0 \u00b1 4.5 min). Furthermore, GGTI2133 (500 nM) and FTI276 (10 nM) significantly inhibited the effects of GGPP and FPP on EFS-induced response. Pretreatment with GGPP (5 \u03bcM) significantly enhanced the EFS response compared with the control and LPS-treated tissues; GGTI2133 (500 nM) significantly inhibited the EFS-induced contractile tension in LPS (300 ng\/ml)-treated tissues, and it was not possible to calculate the t1\/2. In addition, simvastatin and Y27632 (both 1 \u03bcM) were effective in abolishing the contracturant effect of LPS. Our results provide mechanistic evidence for the enhanced bronchoconstriction induced by LPS in human isolated airways, the contribution of Rho\/Ras pathways in this LPS response, and the protective role of statins.<\/jats:p>","DOI":"10.1165\/rcmb.2010-0306oc","type":"journal-article","created":{"date-parts":[[2011,1,28]],"date-time":"2011-01-28T21:20:27Z","timestamp":1296249627000},"page":"704-710","source":"Crossref","is-referenced-by-count":36,"title":["Protein Prenylation Contributes to the Effects of LPS on EFS\u2013Induced Responses in Human Isolated Bronchi"],"prefix":"10.1093","volume":"45","author":[{"given":"Mario","family":"Cazzola","sequence":"first","affiliation":[{"name":"Internal Medicine, University of Rome \u2018Tor Vergata\u2019, Rome, Italy"},{"name":"Pulmonary Rehabilitation, Istituto di Ricovero e Cura a Carattere Scientifico, San Raffaele Pisana, Rome, 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