PMID- 18665050
OWN - NLM
STAT- MEDLINE
DCOM- 20090319
LR  - 20211020
IS  - 1540-0514 (Electronic)
IS  - 1073-2322 (Linking)
VI  - 31
IP  - 3
DP  - 2009 Mar
TI  - Heme oxygenase-1 induction in macrophages by a hemoglobin-based oxygen carrier 
      reduces endotoxin-stimulated cytokine secretion.
PG  - 251-7
LID - 10.1097/SHK.0b013e3181834115 [doi]
AB  - The inflammatory response after an insult may provoke further tissue damage, and 
      the macrophage is central in this pathophysiology. Induction of heme oxygenase-1 
      (HO-1) attenuates postshock organ dysfunction, although the mechanism remains 
      unclear. We hypothesized that HO-1 induction modifies the cytokine profile of 
      LPS-stimulated macrophages. Heme oxygenase-1 was induced in murine and human 
      macrophages with varying concentrations of a hemoglobin-based oxygen carrier 
      (HBOC). Heme oxygenase-1 expression was analyzed by Western blotting of whole 
      cell lysates. Macrophages were pretreated with HBOC for 4 h, then media with LPS 
      were added for up to 24 h. The specific HO-1 inhibitor zinc protoporphyrin (ZnPP) 
      was used to inhibit the effects of HO-1. Supernatants were analyzed for IL-6, 
      IL-10, TNF-alpha, and monocyte chemotactic protein 1 (MCP-1) by enzyme-linked 
      immunosorbent assay. Incubation of cells with HBOC produced a dose-dependent 
      expression of HO-1. Heme oxygenase-1 expression decreased LPS-stimulated 
      secretion of MCP-1, IL-6, IL-10, and TNF-alpha at both 4 and 24 h in murine and 
      human macrophages. The addition of ZnPP to inhibit HO-1 partially restored MCP-1 
      and IL-6 secretion in murine macrophages. Furthermore, immunofluorescent 
      microscopy revealed HBOC-induced HO-1 inhibited LPS-stimulated nuclear 
      translocation of the p65 subunit of nuclear factor-kappaB. In summary, HBOC 
      incubation of macrophages induced HO-1 expression, which reduced LPS-mediated 
      cytokine release, and that MCP-1 and IL-6 secretion could be partially restored 
      with ZnPP. These data encourage continued investigation into the role of HO-1 in 
      protecting against posttraumatic organ dysfunction and the clinical potential of 
      HBOC for HO-1 induction.
FAU - Roach, Jonathan P
AU  - Roach JP
AD  - Department of Surgery, The University of Colorado Denver, Aurora, USA.
FAU - Moore, Ernest E
AU  - Moore EE
FAU - Partrick, David A
AU  - Partrick DA
FAU - Damle, Sagar S
AU  - Damle SS
FAU - Silliman, Christopher C
AU  - Silliman CC
FAU - McIntyre, Robert C Jr
AU  - McIntyre RC Jr
FAU - Banerjee, Anirban
AU  - Banerjee A
LA  - eng
GR  - P50 GM049222/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Shock
JT  - Shock (Augusta, Ga.)
JID - 9421564
RN  - 0 (Blood Substitutes)
RN  - 0 (Cytokines)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Hemoglobins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Protoporphyrins)
RN  - 0 (RELA protein, human)
RN  - 0 (Rela protein, mouse)
RN  - 0 (Transcription Factor RelA)
RN  - 15442-64-5 (zinc protoporphyrin)
RN  - EC 1.14.14.18 (HMOX1 protein, human)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
SB  - IM
MH  - Active Transport, Cell Nucleus/drug effects/immunology
MH  - Animals
MH  - Blood Substitutes/*pharmacology
MH  - Cell Line
MH  - Cell Nucleus/immunology/metabolism
MH  - Cytokines/*biosynthesis/immunology
MH  - Enzyme Induction/drug effects/immunology
MH  - Enzyme Inhibitors/pharmacology
MH  - Heme Oxygenase-1/antagonists & inhibitors/*biosynthesis/immunology
MH  - Hemoglobins/*pharmacology
MH  - Humans
MH  - Lipopolysaccharides/*pharmacology
MH  - Mice
MH  - Protoporphyrins/pharmacology
MH  - Time Factors
MH  - Transcription Factor RelA/immunology/metabolism
EDAT- 2008/07/31 09:00
MHDA- 2009/03/20 09:00
CRDT- 2008/07/31 09:00
PHST- 2008/07/31 09:00 [pubmed]
PHST- 2009/03/20 09:00 [medline]
PHST- 2008/07/31 09:00 [entrez]
AID - 10.1097/SHK.0b013e3181834115 [doi]
PST - ppublish
SO  - Shock. 2009 Mar;31(3):251-7. doi: 10.1097/SHK.0b013e3181834115.