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Morphine stimulates mesangial cell TNF-alpha and nitrite production
A A Kapasi1, N Gibbons, J Mattana
1Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, New York 11040, USA.
Background:
Intravenous opiate abusers are susceptible to develop heroin and HIV-associated nephropathies; however, the role of opiates in the development of these kidney lesions is not clear. Patients with opiate addiction are prone to recurrent infections.
Methods:
The effect of morphine was studied on the generation of TNF-alpha with or without LPS (lipopolysaccharide) by cultured mouse mesangial cells. In addition, the effect of morphine was evaluated on mesangial cell nitrite production. To evaluate the role of opiate receptors, we studied the effect of naloxone and naltrexone on mesangial cell TNF-alpha and nitrite production. To determine the role of TNF-alpha on mesangial cell nitrite production, we examined the effect of anti-TNF-alpha antibody on morphine-induced nitrite production. Assay of TNF-alpha and nitrite production was carried by ELISA and Griess method respectively.
Results:
Morphine alone did not enhance the generation of TNF-alpha by mesangial cells, however, an enhanced (P < 0.001) TNF-alpha production was observed when mesangial cells were first treated with morphine for 18 h and then activated further with LPS. Maximum release of TNF-alpha was seen at a concentration of 10(-12) M of morphine. Opiate receptor antagonists (naloxone and naltrexone) inhibited the effect of morphine. Morphine also amplified (P < 0.0002) the effect of LPS on mesangial cell nitrite production. Anti-TNF-alpha antibody attenuated morphine induced nitrite generation.
Conclusion:
We conclude that morphine stimulates the generation of TNF-infinity by LPS-activated mesangial cells. This effect of morphine seems to be opiate receptor mediated and has a downstream effect in the form of mesangial cell nitrite generation. The present in vitro study provides the basis for a hypothesis that morphine may be playing a role in the development of heroin and HIV-associated nephropathies.
Insights
Morphine stimulates kidney cells to produce tumor necrosis factor-alpha (TNF-α) and nitrite, potentially contributing to heroin and HIV-associated nephropathies. This effect is mediated by opiate receptors and involves TNF-α.
Area of Science:
- Nephrology
- Immunology
- Pharmacology
Background:
- Intravenous opiate abusers are at risk for heroin and HIV-associated nephropathies.
- The precise role of opiates in kidney lesion development remains unclear.
- Opiate-addicted patients frequently experience recurrent infections.
Purpose of the Study:
- To investigate the effect of morphine on tumor necrosis factor-alpha (TNF-α) and nitrite production in cultured mouse mesangial cells.
- To determine the involvement of opiate receptors in morphine's effects on mesangial cells.
- To elucidate the role of TNF-α in morphine-induced nitrite production.
Main Methods:
- Cultured mouse mesangial cells were treated with morphine, lipopolysaccharide (LPS), or both.
- The effects of opiate receptor antagonists (naloxone, naltrexone) and anti-TNF-α antibody were assessed.
- TNF-α and nitrite levels were quantified using ELISA and the Griess method, respectively.
Main Results:
- Morphine alone did not increase TNF-α production, but enhanced it when cells were pre-treated with morphine followed by LPS (P < 0.001).
- Morphine also amplified LPS-induced nitrite production in mesangial cells (P < 0.0002).
- Opiate antagonists inhibited morphine's effects, and anti-TNF-α antibody attenuated morphine-induced nitrite generation.
Conclusions:
- Morphine stimulates TNF-α generation in LPS-activated mesangial cells via opiate receptors, leading to increased nitrite production.
- This in vitro evidence suggests morphine may contribute to the pathogenesis of heroin and HIV-associated nephropathies.
- The findings provide a basis for further investigation into opiate-induced kidney damage.