PMID- 19032979 OWN - NLM STAT- MEDLINE DCOM- 20090415 LR - 20211020 IS - 0306-4522 (Print) IS - 0306-4522 (Linking) VI - 158 IP - 2 DP - 2009 Jan 23 TI - Monocyte chemoattractant protein-1 in the choroid plexus: a potential link between vascular pro-inflammatory mediators and the CNS during peripheral tissue inflammation. PG - 885-95 LID - 10.1016/j.neuroscience.2008.10.047 [doi] AB - During peripheral tissue inflammation, inflammatory processes in the CNS can be initiated by blood-borne pro-inflammatory mediators. The choroid plexus, the site of cerebrospinal fluid (CSF) production, is a highly specialized interface between the vascular system and CNS, and thus, this structure may be an important element in communication between the vascular compartment and the CNS during peripheral tissue inflammation. We investigated the potential participation of the choroid plexus in this process during peripheral tissue inflammation by examining expression of the small inducible cytokine A2 (SCYA2) gene which codes for monocyte chemoattractant protein-1 (MCP-1). MCP-1 protein was previously reported to be induced in a variety of cells during peripheral tissue inflammation. In the basal state, SCYA2 is highly expressed in the choroid plexus as compared with other rat CNS tissues. During hind paw inflammation, SCYA2 expression was significantly elevated in choroid plexus, whereas it remained unchanged in a variety of brain regions. The SCYA2-expressing cells were strongly associated with the choroid plexus as vascular depletion of blood cells by whole-body saline flush did not significantly alter SCYA2 expression in the choroid plexus. In situ hybridization suggested that the SCYA2-expressing cells were localized to the choroid plexus stroma. To elucidate potential molecular mechanisms of SCYA2 increase, we examined genes in the nuclear factor-kappa B (NF-kappaB) signaling cascade including tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and inhibitor of kappa B alpha (IkappaBalpha) in choroid tissue. Given that we also detected increased levels of MCP-1 protein by ELISA, we sought to identify potential downstream targets of MCP-1 and observed altered expression levels of mRNAs encoding tight junction proteins TJP2 and claudin 5. Finally, we detected a substantial up-regulation of the transcript encoding endothelial leukocyte adhesion molecule 1 (E-selectin), a molecule which could participate in leukocyte recruitment to the choroid plexus along with MCP-1. Together, these results suggest that profound changes occur in the choroid plexus during peripheral tissue inflammation, likely initiated by blood-borne inflammatory mediators, which may modify events in CNS. FAU - Mitchell, K AU - Mitchell K AD - Neurobiology and Pain Therapeutics Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Building 49, Room 1C20, 49 Convent Drive, MSC 4410, Bethesda, MD 20892-4410, USA. FAU - Yang, H-Y T AU - Yang HY FAU - Berk, J D AU - Berk JD FAU - Tran, J H AU - Tran JH FAU - Iadarola, M J AU - Iadarola MJ LA - eng GR - Z01 DE000688-11/ImNIH/Intramural NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Intramural DEP - 20081107 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Cell Adhesion Molecules) RN - 0 (Chemokine CCL2) RN - 0 (Cytokines) RN - 0 (RNA, Messenger) RN - 9000-07-1 (Carrageenan) RN - EC 3.4.22.36 (Caspase 1) SB - IM MH - Analysis of Variance MH - Animals MH - Brain/metabolism/*pathology MH - Carrageenan MH - Caspase 1/genetics/metabolism MH - Cell Adhesion Molecules/genetics/metabolism MH - Chemokine CCL2/genetics/*metabolism MH - Choroid Plexus/*metabolism MH - Cytokines/genetics/*metabolism MH - Disease Models, Animal MH - Gene Expression Regulation/drug effects/*physiology MH - Inflammation/chemically induced/*pathology MH - Male MH - RNA, Messenger/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Time Factors PMC - PMC2668531 MID - NIHMS94269 EDAT- 2008/11/27 09:00 MHDA- 2009/04/16 09:00 PMCR- 2010/01/23 CRDT- 2008/11/27 09:00 PHST- 2008/07/07 00:00 [received] PHST- 2008/10/17 00:00 [revised] PHST- 2008/10/28 00:00 [accepted] PHST- 2008/11/27 09:00 [entrez] PHST- 2008/11/27 09:00 [pubmed] PHST- 2009/04/16 09:00 [medline] PHST- 2010/01/23 00:00 [pmc-release] AID - S0306-4522(08)01590-X [pii] AID - 10.1016/j.neuroscience.2008.10.047 [doi] PST - ppublish SO - Neuroscience. 2009 Jan 23;158(2):885-95. doi: 10.1016/j.neuroscience.2008.10.047. Epub 2008 Nov 7.