PMID- 19695100
OWN - NLM
STAT- MEDLINE
DCOM- 20091103
LR  - 20211020
IS  - 1744-8069 (Electronic)
IS  - 1744-8069 (Linking)
VI  - 5
DP  - 2009 Aug 20
TI  - Tumor necrosis factor-alpha (TNF-alpha) enhances functional thermal and chemical 
      responses of TRP cation channels in human synoviocytes.
PG  - 49
LID - 10.1186/1744-8069-5-49 [doi]
AB  - BACKGROUND: We have shown functional expression of several TRP channels on human 
      synovial cells, proposing significance in known calcium dependent proliferative 
      and secretory responses in joint inflammation. The present study further 
      characterizes synoviocyte TRP expression and activation responses to thermal and 
      osmotic stimuli after pre-treatment with proinflammatory mediator tumor necrosis 
      factor alpha (TNF-alpha, EC50 1.3221 x 10(-10) g/L). RESULTS: Fluorescent imaging 
      of Fura-2 loaded human SW982 synoviocytes reveals immediate and delayed cytosolic 
      calcium oscillations elicited by (1) TRPV1 agonists capsaicin and resiniferatoxin 
      (20-40% of cells), (2) moderate and noxious temperature change, and (3) osmotic 
      stress TRPV4 activation (11.5% of cells). TNF-alpha pre-treatment (1 ng/ml, 8-16 
      hr) significantly increases (doubles) capsaicin responsive cell numbers and 
      [Ca2+]i spike frequency, as well as enhances average amplitude of temperature 
      induced [Ca2+]i responses. With TNF-alpha pre-treatment for 8, 12, and 16 hr, 
      activation with 36 or 45 degree bath solution induces bimodal [Ca2+]i increase 
      (temperature controlled chamber). Initial temperature induced rapid transient 
      spikes and subsequent slower rise reflect TRPV1 and TRPV4 channel activation, 
      respectively. Only after prolonged TNF-alpha exposure (12 and 16 hr) is 
      recruitment of synoviocytes observed with sensitized TRPV4 responses to 
      hypoosmolarity (3-4 fold increase). TNF-alpha increases TRPV1 (8 hr peak) and 
      TRPV4 (12 hr peak) immunostaining, mRNA and protein expression, with a TRPV1 
      shift to membrane fractions. CONCLUSION: TNF-alpha provides differentially 
      enhanced synoviocyte TRPV1 and TRPV4 expression and [Ca2+]i response dependent on 
      the TRP stimulus and time after exposure. Augmented relevance of TRPV1 and TRPV4 
      as inflammatory conditions persist would provide calcium mediated cell signaling 
      required for pathophysiological responses of synoviocytes in inflammatory pain 
      states.
FAU - Kochukov, Mikhail Y
AU  - Kochukov MY
AD  - Department of Neuroscience and Cell Biology, University of Texas Medical Branch, 
      Galveston, Texas, USA. mykochuk@utmb.edu
FAU - McNearney, Terry A
AU  - McNearney TA
FAU - Yin, Huaizhi
AU  - Yin H
FAU - Zhang, Liping
AU  - Zhang L
FAU - Ma, Fei
AU  - Ma F
FAU - Ponomareva, Larissa
AU  - Ponomareva L
FAU - Abshire, Sarah
AU  - Abshire S
FAU - Westlund, Karin N
AU  - Westlund KN
LA  - eng
GR  - NS 32778/NS/NINDS NIH HHS/United States
GR  - NS11255/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090820
PL  - United States
TA  - Mol Pain
JT  - Molecular pain
JID - 101242662
RN  - 0 (Diterpenes)
RN  - 0 (Sensory System Agents)
RN  - 0 (TRPV Cation Channels)
RN  - 0 (Transient Receptor Potential Channels)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - A5O6P1UL4I (resiniferatoxin)
RN  - S07O44R1ZM (Capsaicin)
SB  - IM
MH  - Capsaicin/pharmacology
MH  - Cell Line
MH  - Diterpenes/pharmacology
MH  - Gene Expression/drug effects
MH  - Humans
MH  - Osmotic Pressure/drug effects
MH  - Sensory System Agents/pharmacology
MH  - Synovial Membrane/*cytology/*metabolism
MH  - TRPV Cation Channels/agonists/genetics/metabolism
MH  - Temperature
MH  - Transient Receptor Potential Channels/agonists/genetics/*metabolism
MH  - Tumor Necrosis Factor-alpha/*pharmacology
PMC - PMC3152771
EDAT- 2009/08/22 09:00
MHDA- 2009/11/05 06:00
PMCR- 2009/08/20
CRDT- 2009/08/22 09:00
PHST- 2009/03/10 00:00 [received]
PHST- 2009/08/20 00:00 [accepted]
PHST- 2009/08/22 09:00 [entrez]
PHST- 2009/08/22 09:00 [pubmed]
PHST- 2009/11/05 06:00 [medline]
PHST- 2009/08/20 00:00 [pmc-release]
AID - 1744-8069-5-49 [pii]
AID - 10.1186/1744-8069-5-49 [doi]
PST - epublish
SO  - Mol Pain. 2009 Aug 20;5:49. doi: 10.1186/1744-8069-5-49.