International immunopharmacology
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Int. Immunopharmacol. · Feb 2008
Role of kinin B1 and B2 receptors in a rat model of neuropathic pain.
Kinin B1 and B2 receptor (R) gene expression (mRNA) is increased in the sensory system after peripheral nerve injury. This study measured the densities of B1R and B2R binding sites in the spinal cord and dorsal root ganglia (DRG) by quantitative autoradiography, and evaluated the effects of two selective non-peptide antagonists at B1R (LF22-0542) and B2R (LF16-0687) on pain behavior after partial ligation of the left sciatic nerve. Increases of B1R binding sites were seen in superficial laminae of the ipsi- and contralateral spinal cord at 2 and 14 days while B2R binding sites were increased on the ipsilateral side at 2 days and on both sides at 14 days. ⋯ At day 21 after sciatic nerve ligation, thermal hyperalgesia was blocked by LF22-0542 (10 mg/kg, s.c.) and LF16-0687 (3 mg/kg, s.c.), yet both antagonists had no effect on tactile and cold allodynia. Data highlight the implication of both kinin receptors in thermal hyperalgesia but not in tactile and cold allodynia associated with peripheral nerve injury. Hence LF22-0542 and LF16-0687 present therapeutic potential for the treatment of some aspects of neuropathic pain.
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Int. Immunopharmacol. · Jan 2008
Comparative StudyAnti-tumor metastatic activity of beta-glucan purified from mutated Saccharomyces cerevisiae.
The beta-glucans isolated from Saccharomyces cerevisiae (S. cerevisiae) enhance the innate immune system, but there is little evidence for its antitumor activity. To examine the antitumor and immunostimulating activities of beta-glucan (IS-2) purified from mutated S. cerevisiae, we made an experiment on innate immune response against metastasis of cancer cells by comparing with the beta-glucan from wild-type S. cerevisiae. In experimental lung metastasis of colon 26-M3.1 carcinoma or B16-BL6 melanoma cells, prophylactic administration of beta-glucan purified from mutated S. cerevisiae significantly inhibited lung metastasis in a dose-dependent manner. ⋯ In an assay for natural killer (NK) cell activity, IS-2 (20 microg/mouse, i.v.) significantly augmented NK cytotoxicity against Yac-1 tumor cells at 2 days after IS-2 treatment. The depletion of NK cells by injection of rabbit anti-asialo GM1 serum abolished the inhibitory effect of IS-2 on lung metastasis of colon 26-M3.1 cells. These data suggest that IS-2 inhibits tumor metastasis via activation of macrophages and NK cells.
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Int. Immunopharmacol. · Dec 2007
ReviewA journey with Tony Hugli up the inflammatory cascade towards the auto-digestion hypothesis.
My association with Tony Hugli, long-term editor of Immunopharmacology and International Immunopharmacology, came about by a specific and long-standing problem in inflammation research. What is the trigger mechanism of inflammation in physiological shock? This is an important clinical problem due to the high mortality associated with physiological shock. We joined forces in the search of the answer to this question for more than a decade. ⋯ Thus, our journey led to a new hypothesis, which is potentially of fundamental importance for death by multi-organ failure. The auto-digestion hypothesis is in line with the century old observation that the intestine plays a special role on shock - indeed it is the organ for digestion. Auto-digestion may be the prize to pay for life-long nutrition.
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Int. Immunopharmacol. · Dec 2007
Sinomenine inhibits activation of rat retinal microglia induced by advanced glycation end products.
Diabetic retinopathy involves an inflammatory response in the retina characterized by an increase in inflammatory cytokines and activation of microglia. The degree of microglia activation may influence the extent of retina injury following an inflammatory stimulus. Cytokines, released by activated microglia, regulate the influx of inflammatory cells to the damaged area. ⋯ AGEs treatment induced a significant release of TNF alpha, IL-1 beta, and IL-6 from retinal microglia. Sinomenine could inhibit release of these cytokines. Sinomenine attenuated ROS production in a dose-dependent fashion and reduced the nuclear translocation of NF-kB p65 in AGEs-activated retinal microglia in culture.
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Int. Immunopharmacol. · Nov 2007
Apoptosis of murine lupus T cells induced by the selective cyclooxygenase-2 inhibitor celecoxib: molecular mechanisms and therapeutic potential.
Upregulation of cyclooxygenase (COX)-2 in T cells from patients with systemic lupus erythematosus (SLE) is associated with their resistance to functional inactivation (anergy) and to activation-induced cell death through apoptosis. It has been demonstrated that celecoxib, a selective COX-2 inhibitor, can enhance apoptosis of human lupus T cells. The present study was undertaken to investigate whether COX-2 expression is also upregulated in T cells from the lupus-prone BXBS strain of mice and if murine lupus is modified by celecoxib. ⋯ These data combine to suggest that celecoxib mainly uses the mitochondrial pathway rather than FADD pathway to trigger apoptosis of COX-2 expressing murine lupus T cells. Intragastric administration of celecoxib (40 mg/kg/day for 60 days) in 6-month-old male BXSB mice effectively limited the production of serum antibodies against dsDNA. Our data suggest that celecoxib may have a beneficial effect in treating autoimmune diseases such as SLE through inducing apoptosis of autoreactive T cells.