BACKGROUND: The nonparenchymal cells of the liver have been suggested to play a significant role in the inflammatory processes observed in the development and/or progression of alcoholic liver disease. Our laboratories have shown that malondialdehyde-acetaldehyde (MAA)-modified proteins can induce immune responses, cytokine/chemokine secretion, and antigen processing and presentation by liver sinusoidal endothelial cells (SECs). Another molecule that has been shown to induce similar types of responses in Kupffer cells (KCs) is lipopolysaccharide (LPS). Because these materials induce similar responses, it was the purpose of this study to investigate the relationship between LPS and MAA-modified proteins in the development of proinflammatory responses by SECs and KCs. METHODS: For these studies, SECs and KCs were isolated from chow-fed, pair-fed, and ethanol-fed rats. Cells were stimulated with media alone, bovine serum albumin (Alb), or MAA-modified Alb (MAA-Alb) in the presence or absence of LPS 1 ng/ml, and the supernatants were assayed by enzyme-linked immunosorbent assay for tumor necrosis factor alpha, macrophage chemotactic protein 1, and macrophage inhibitory protein. RESULTS: All three cytokines/chemokines were 3 to 5 times higher when SECs or KCs were stimulated by MAA-Alb in the presence of LPS, in contrast to cells stimulated with Alb or media in the presence of LPS. Chronic ethanol consumption (6 weeks) had variable effects on the secretion of these cytokines/chemokines but in general did not alter the increased secretion in response to MAA-Alb in the presence of LPS. CONCLUSIONS: These studies strongly suggest that the sensitization of SECs and KCs by LPS plays a significant role in the development and/or progression of alcoholic liver disease, and the subsequent activation by MAA-modified proteins may be a mechanism by which proinflammatory processes are initiated.
BACKGROUND: The nonparenchymal cells of the liver have been suggested to play a significant role in the inflammatory processes observed in the development and/or progression of alcoholic liver disease. Our laboratories have shown that malondialdehyde-acetaldehyde (MAA)-modified proteins can induce immune responses, cytokine/chemokine secretion, and antigen processing and presentation by liver sinusoidal endothelial cells (SECs). Another molecule that has been shown to induce similar types of responses in Kupffer cells (KCs) is lipopolysaccharide (LPS). Because these materials induce similar responses, it was the purpose of this study to investigate the relationship between LPS and MAA-modified proteins in the development of proinflammatory responses by SECs and KCs. METHODS: For these studies, SECs and KCs were isolated from chow-fed, pair-fed, and ethanol-fed rats. Cells were stimulated with media alone, bovineserum albumin (Alb), or MAA-modified Alb (MAA-Alb) in the presence or absence of LPS 1 ng/ml, and the supernatants were assayed by enzyme-linked immunosorbent assay for tumor necrosis factor alpha, macrophage chemotactic protein 1, and macrophage inhibitory protein. RESULTS: All three cytokines/chemokines were 3 to 5 times higher when SECs or KCs were stimulated by MAA-Alb in the presence of LPS, in contrast to cells stimulated with Alb or media in the presence of LPS. Chronic ethanol consumption (6 weeks) had variable effects on the secretion of these cytokines/chemokines but in general did not alter the increased secretion in response to MAA-Alb in the presence of LPS. CONCLUSIONS: These studies strongly suggest that the sensitization of SECs and KCs by LPS plays a significant role in the development and/or progression of alcoholic liver disease, and the subsequent activation by MAA-modified proteins may be a mechanism by which proinflammatory processes are initiated.
Authors: Geoffrey M Thiele; Michael J Duryee; Monte S Willis; Dean J Tuma; Stanley J Radio; Carlos D Hunter; Courtney S Schaffert; Lynell W Klassen Journal: Alcohol Clin Exp Res Date: 2010-09-22 Impact factor: 3.455
Authors: Kamaljit K Chaudhry; Geetha Samak; Pradeep K Shukla; Hina Mir; Ruchika Gangwar; Bhargavi Manda; Toyohi Isse; Toshihiro Kawamoto; Mikko Salaspuro; Pertti Kaihovaara; Paula Dietrich; Ioannis Dragatsis; Laura E Nagy; Radha Krishna Rao Journal: Alcohol Clin Exp Res Date: 2015-07-14 Impact factor: 3.455
Authors: Ted R Mikuls; Michael J Duryee; Rafid Rahman; Daniel R Anderson; Harlan R Sayles; Andrew Hollins; Kaleb Michaud; Frederick Wolfe; Geoffrey E Thiele; Jeremy Sokolove; William H Robinson; Nithya Lingampalli; Anthony P Nicholas; Geoffrey A Talmon; Kaihong Su; Matthew C Zimmerman; Lynell W Klassen; Geoffrey M Thiele Journal: Rheumatology (Oxford) Date: 2017-10-01 Impact factor: 7.580
Authors: Courtney S Schaffert; Michael J Duryee; Robert G Bennett; Amy L DeVeney; Dean J Tuma; Peter Olinga; Karen C Easterling; Geoffrey M Thiele; Lynell W Klassen Journal: Am J Physiol Gastrointest Liver Physiol Date: 2010-07-01 Impact factor: 4.052
Authors: Courtney S Schaffert; Michael J Duryee; Carlos D Hunter; Bartlett C Hamilton; Amy L DeVeney; Mary M Huerter; Lynell W Klassen; Geoffrey M Thiele Journal: World J Gastroenterol Date: 2009-03-14 Impact factor: 5.742