PMID- 15253719 OWN - NLM STAT- MEDLINE DCOM- 20041101 LR - 20061115 IS - 0085-2538 (Print) IS - 0085-2538 (Linking) VI - 66 IP - 2 DP - 2004 Aug TI - Proximal tubule cells stimulated by lipopolysaccharide inhibit macrophage activation. PG - 655-62 AB - BACKGROUND: Tubule cells can produce a variety of cytokines, extracellular matrix (ECM) components, and adhesion molecules in vitro and in vivo. It is generally assumed that stimulated tubule cells are proinflammatory and at least partially responsible for interstitial inflammation. However, the overall effect of tubular cells on interstitial cells is unknown. In this study, pro- and anti-inflammatory cytokine production and net effects on macrophages of tubule cells activated by lipopolysaccharide (LPS) were examined. METHODS: Tubule cells stimulated with LPS expressed tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-12, monocyte chemoattractant protein-1 (MCP-1), IL-10, and transforming growth factor-beta (TGF-beta). Conditioned media were collected from confluent monolayers of rat tubule cells stimulated, or not, by LPS for 4 and 18 hours, respectively. Macrophages were cultured with conditioned media and/or LPS (0.5 microg/mL) for 18 hours. RESULTS: TNF-alpha and IL-lbeta mRNA of macrophages stimulated by LPS increased more than fivefold when cultured with control conditioned media from unstimulated tubule cells. Surprisingly, TNF-alpha and IL-lbeta levels of macrophages stimulated by LPS were not increased when cultured with conditioned media from activated tubule cells. Neutralizing antibodies to IL-10 and TGF-beta were used to define the inhibitory component(s) in conditioned medium. Anti-IL-10, but not anti-TGF-beta, abolished partially the inhibitory effects of conditioned media on macrophages. CONCLUSION: Tubule cells produce both pro- and anti-inflammatory cytokines and the net effect, partially explained by IL-10, of tubule cells activated with LPS is to inhibit activity of macrophages. Thus, the net effect of activated tubule cells on interstitial pathology may in certain circumstances, be anti- rather than pro-inflammatory. FAU - Wang, Yiping AU - Wang Y AD - Center for Transplantation and Renal Research, The University of Sydney at Westmead Millenium Institute,Westmead, Sydney, Australia. Yiping_Wang@wsahs.nsw.gov.au FAU - Tay, Yuet-Ching AU - Tay YC FAU - Harris, David C H AU - Harris DC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Kidney Int JT - Kidney international JID - 0323470 RN - 0 (Culture Media, Conditioned) RN - 0 (Cytokines) RN - 0 (Lipopolysaccharides) SB - IM MH - Animals MH - Cell Communication/immunology MH - Cells, Cultured MH - Culture Media, Conditioned/pharmacology MH - Cytokines/genetics MH - Gene Expression/immunology MH - Kidney Tubules, Proximal/*cytology/*drug effects/immunology MH - Lipopolysaccharides/*pharmacology MH - Macrophages/*cytology/*immunology MH - Male MH - Paracrine Communication/immunology MH - Rats MH - Rats, Wistar EDAT- 2004/07/16 05:00 MHDA- 2004/11/02 09:00 CRDT- 2004/07/16 05:00 PHST- 2004/07/16 05:00 [pubmed] PHST- 2004/11/02 09:00 [medline] PHST- 2004/07/16 05:00 [entrez] AID - S0085-2538(15)50094-X [pii] AID - 10.1111/j.1523-1755.2004.00786.x [doi] PST - ppublish SO - Kidney Int. 2004 Aug;66(2):655-62. doi: 10.1111/j.1523-1755.2004.00786.x.