PMID- 7591712
OWN - NLM
STAT- MEDLINE
DCOM- 19951207
LR  - 20190920
IS  - 0162-3109 (Print)
IS  - 0162-3109 (Linking)
VI  - 30
IP  - 1
DP  - 1995 Jun
TI  - Modification of tumor necrosis factor-alpha (TNF-alpha) production by the 
      Na(+)-dependent HCO3- cotransport in lipopolysaccharide-activated human 
      monocytes.
PG  - 41-50
AB  - Tumor necrosis factor-alpha (TNF-alpha) is produced and secreted from monocytes 
      in response to activation with lipopolysaccharide (LPS). The role of Na+ and 
      HCO3- in the production of TNF-alpha by monocytes was investigated; it was 
      observed that replacement of Na+ in the culture medium with sucrose or choline 
      chloride inhibited TNF-alpha production completely. The addition of Na+ to 
      Na(+)-free culture medium restored TNF-alpha production with an EC50 value of 35 
      mmol/l. The amiloride analog 5-(N-ethyl-N-isopropyl)amiloride (EIPA), an 
      inhibitor of the Na+/H+ antiporter, inhibited TNF-alpha production with an EC50 
      of 3.3 microM. Without HCO3- in the culture medium TNF-alpha production was 
      inhibited by 92%. Total protein synthesis was inhibited by 85% in the absence of 
      Na+ but did not change in the absence of bicarbonate in the culture medium. 
      Intracellular pH (pHi) which increased from 6.90 in control monocyte to 7.40 in 
      response to activation with LPS was abrogated to pHi of 6.95 in the absence of 
      Na+ but did not change in the absence of HCO3- in the culture medium. In the 
      presence of 100 microM phloretin or DIDS the pHi of activated monocyte was 
      reduced to control value, TNF-alpha production was inhibited completely and total 
      protein synthesis was inhibited by 61%. These data suggest that (1) TNF-alpha 
      production, as other proteins, is dependent on the pHi of monocytes,and (2) 
      TNF-alpha production, in contrast to total protein, is modulated by 
      Na(+)-dependent HCO3-.
FAU - Orlinska, U
AU  - Orlinska U
AD  - Inflammatory Diseases Research, Du Pont Merck Pharmaceutical Co., Wilmington, DE 
      19880, USA.
FAU - Newton, R C
AU  - Newton RC
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Immunopharmacology
JT  - Immunopharmacology
JID - 7902474
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Bicarbonates)
RN  - 0 (Carrier Proteins)
RN  - 0 (Culture Media)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Sodium-Bicarbonate Symporters)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 7DZO8EB0Z3 (Amiloride)
RN  - 9NEZ333N27 (Sodium)
RN  - Q1O6DSW23R (4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid)
RN  - S5J5OE47MK (Phloretin)
RN  - VW50CE070T (ethylisopropylamiloride)
SB  - IM
MH  - 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid/pharmacology
MH  - Adjuvants, Immunologic/pharmacology
MH  - Amiloride/analogs & derivatives/pharmacology
MH  - Bicarbonates/metabolism/pharmacology
MH  - Carrier Proteins/*pharmacology
MH  - Culture Media/pharmacology
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Kinetics
MH  - Lipopolysaccharides/*pharmacology
MH  - Macrophage Activation/*drug effects
MH  - Monocytes/drug effects/*metabolism
MH  - Phloretin/pharmacology
MH  - Protein Biosynthesis
MH  - Sodium/deficiency/pharmacology
MH  - Sodium-Bicarbonate Symporters
MH  - Tumor Necrosis Factor-alpha/*biosynthesis/drug effects
EDAT- 1995/06/01 00:00
MHDA- 1995/06/01 00:01
CRDT- 1995/06/01 00:00
PHST- 1995/06/01 00:00 [pubmed]
PHST- 1995/06/01 00:01 [medline]
PHST- 1995/06/01 00:00 [entrez]
AID - 016231099500006F [pii]
AID - 10.1016/0162-3109(95)00006-f [doi]
PST - ppublish
SO  - Immunopharmacology. 1995 Jun;30(1):41-50. doi: 10.1016/0162-3109(95)00006-f.