S100B, a 21kDa cytosolic calcium-binding protein of the EF-hand type, present in high abundance in the brain, stimulates inflammatory responses in different cellular types inside and outside the central nervous system. Most of extracellular S100B effects are mediated by Receptor for Advanced Glycation End-products (RAGE). RAGE is highly expressed in lung by Alveolar Type-I (AT-I) cells and its activation contributes to ALI/ARDS pathogenesis. In this in-vitro study, we tested the hypothesis that S100B (0.002μg/L, 0.02μg/L, 0.5μg/L, 5μg/L) stimulates an ATI-derived cell line (R3/1) to secrete inflammatory mediators involved in lung inflammation. Our main result is that S100B stimulates R3/1 cells to secrete TNF-alpha and IL-6 (well-known pro-inflammatory cytokines in lung inflammation and neurogenic pulmonary edema), but not sICAM-1, CINC-1 or CINC-3. Soluble RAGE (sRAGE) reduced SlOOB-dependent secretion of TNF-alpha but did not decrease S100B-dependent secretion of IL-6. Moreover, in absence of S100B, sRAGE enhanced IL-6 release. This study demonstrates that in vitro S100B dose-dependently stimulated R3/1 cells, to enhance the secretion of TNF-alpha and IL-6; S100B pro-inflammatory activity might be mediated at least in part by RAGE. Besides acting as decoy receptor, sRAGE could have pro-inflammatory properties.

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THERE is at present good evidence that urethane (ethyl carbamate) is a tumourinducing agent with a broad spectrum of activity. However, since the first observation of Nettleship and Henshaw (1943), lung seems to be the tissue most susceptible to the carcinogenic action of this chemical.In experiments previously reported (Fiore-Donati et al., 1961b) we observed that the administration of urethane to lactating mice gave rise to pulmonary adenomas in a high percentage of the offspring. A more extensive study, which is reported here, was designed to add new information on the influence of the age of animals and route of administration of urethane on lung carcinogenesis in mice.MATERIAL AND METHODS Swiss mice of both sexes, originally obtained from ARSAL Co. Roma, and bred in this laboratory since 1959, were used. The animals were housed in wooden cages in a temperature-controlled room at 21-23°C. ARSAL mouse diet and water were provided ad libitum. Urethane was obtained from Carlo Erba S.p.A., Milano.The experiments were set up as follows Experimental group 1.-Female mice received at the 1st, 3rd, and 5th day after parturition 30 mg. of urethane by stomach tube in 0-25 ml. of distilled water. The young were killed at 20, 45, and 90 days of age. Another group of lactating mothers received 5 or 10 doses of urethane starting from the 1st or 3rd day after parturition, and the young were killed at 210 days of age. When the litters were large, the newborn exceeding the number of six were killed at birth in order to uniform the suckling of all litters.Experimental group 2.-To exclude the possibilitv of contamination of the suckling mice from sources other than maternal milk, urethane was given in this experiment to the male parents of the litters. Five doses of 30 mg. of urethane were given by stomach tube at the 1st, 3rd, 5th, 7th, and 9th day after birth of the litters. The urethane-treated parent was caged together with the litter and the lactating female until the young were weaned. The young were killed at 45, 90, and 210 days of age.Experimental group 3.-Newborn animals less than 24 hours old were injected subcutaneously in the interscapular region with a single dose of 2 mg. of urethane in 0 05 ml. of distilled water (approximately 1 mg. /g. of body weight). They were killed at 20, 45, 90, and 210 days of age.Experimental group 4.-Adult mice, 45 days old, were injected subcutaneouslv

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