Table 2.
Summary of Conflicting Reports on the Role of HO-1 in Dendritic Cell Maturation
| Culture conditions | Maturation stimulusb | Key findings | References |
|---|---|---|---|
| Rat BMDC: | High HO-1 expression in immature DC | (39) | |
| GM-CSF (1.5 ng/ml)a | TNF-a | ||
| IL-4 (4 ng/ml)a | Poly(I:C) | Stimulus-induced maturation (MHCII, CD80, CD86 and IL-12, 1L-6, TNF-α secretion) inhibits HO-1 expression | |
| LPS | |||
| Human MDDC: | CpG | ||
| GM-CSF (500 UL/ml) | CD40L | HO-1 induction with CoPP or IL-10 blocks DC maturation, but preserves IL-10 secretion | |
| IL-4 (40 ng/ml) | |||
| Murine BMDC: | LPS | No reduction in HO-1 expression after stimulation with LPS [as in Ref. (39)] at low GM-CSF concentration | (131) |
| 100 U/ml GM-CSF | |||
| 800 U/ml GM-CSF | Increased GM-CSF concentration or addition of IL-4 generated results similar to those previously reported (39) | ||
| 100 U/ml GM-CSF + 10 ng/ml IL-4 | IL-4 significantly increases LPS-induced maturation (i.e., MHCII and CD86) | ||
| Human MDDC: | LPS blocks, but CoPP or CORM2 rescues, HO-1 expression in mature DC | (136) | |
| GM-CSF (1000 U/ml) | CO (CORM2 or CoPP) blocks TLR3 and TLR4 induced: | ||
| IL-4 (40 ng/ml) | Phenotypic maturation (CD80, CD86) | ||
| LPS | Pro-inflammatory cytokine section (IL-12p70, IL-12p40, IL-23) | ||
| Murine BMDC: | Poly(I:C) | T-cell proliferation in MLR | |
| GM-CSF (10 ng/ml from COS cells)a | Biliverdin, bilirubin, deferoxamine, or heme have no affect on DC maturation | ||
| CO preserves IL-10 secretion in mature DC | |||
| Rat BMDC: | LPS | LPS induces HO-1 expression and DC maturation (MHCII, CD80, CD86) | (89) |
| IL-4 (4 ng/ml) | |||
| GM-CSF (1.5 ng/ml) | CoPP pretreatment prevents LPS-induced DC maturation | ||
| Murine MDDC: | LPS | CoPP prevents DC differentiation from monocytes and prevents DC phenotypic maturation (MHCII, CD86, CD83), T-cell proliferation in MLR, IL-12p40, IL-12p70, and TNF-α (but not IL-10) secretion | (97) |
| GM-CSF (10 ng/ml) | |||
| IL-4 (10 ng/ml) | CoPP inhibits LPS-induced maturation of BMDC independent of HO-1 expression (in HO-1−/− and HO-1+/+ BMDC) by directly activating STAT-3 (132, 137) | ||
| HO-1+/+ and HO-1−/− murine BMDC: | LPS | IL-10-mediated induction of HO-1 expression in BMDC is STAT-3 dependent | (105) |
| GM-CSF (10 ng/ml) | No reduction in HO-1 expression after stimulation with LPS [as in Ref. (39)] |
Differences in the expression of HO-1 with respect to maturation stimuli may be a result of different culture conditions. Evaluating this possibility is problematic because many authors do not indicate the biological activities of the cytokines used to propagate the BMDC. Murine BMDC propagated with GM-CSF±IL-4 represent the CD8− DC subpopulation in the mouse spleen (155), while those propagated with Flt3-ligand more closely resemble CD8+ DC based on phenotype and the ability to cross-present antigens (46, 120).
From the culture supernatant of COS cells transfected with rat IL-4 or GM-CSF cDNA
Stimulus and specificity: TNF-α, Th1 inflammatory cytokine; Poly(I:C), polyinosinic-polycytidylic acid, TLR3; LPS, TLR4; CpG, cytosine phosphate guanine, TLR9; CD40L, lymphocyte stimulus.
BMDC, bone marrow-derived dendritic cell; CO, carbon monoxide; CORM2, CO releasing molecule 2; tricarbonyldichlororuthenium II; DC, dendritic cell; GM-CSF, granulocyte macrophage colony-stimulating factor; LPS, lipopolysaccharide; MDDC, monocyte-derived dendritic cell; MHC, major histocompatibility complex; STAT-3, signal transducer and activator of transcription-3; TLR, toll-like receptor.