Inhibition by interleukin-10 of inducible cyclooxygenase expression in lipopolysaccharide-stimulated monocytes: its underlying mechanism in comparison with interleukin-4

Niiro, Hiroaki; Otsuka, Takeshi; Tanabe, Tadashi; Hara, Shuntaro; Kuga, Seiji; Nemoto, Yoshiaki; Tanaka, Yosuke; Nakashima, Hitoshi; Kitajima, Shigetaka; Abe, Masajiro

doi:10.1182/blood.v85.12.3736.bloodjournal85123736

Cited by 94 publications

(27 citation statements)

References 43 publications

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“…A previous report has shown that BA inhibits the expression of cyclooxygenase 2 (COX-2) expression in cultures of human peripheral blood mononuclear cells, leading to a decrease in PGE2 production [22]. The increase in IL-10 induced by BA described in our study may be related to the inhibition of PGE 2 production, another inflammatory mediator in LPS-challenged mice, since IL-10 is known to inhibit COX2 expression by LPS-stimulated monocytes [23]. Thus, we are establishing the role of another molecule involved in the anti-inflammatory activity produced by BA.…”

Section: Discussionsupporting

confidence: 64%

Potent anti-inflammatory activity of betulinic acid treatment in a model of lethal endotoxemia

Costa

Barbosa-Filho

Maia

et al. 2014

International Immunopharmacology

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Betulinic acid (BA) is a lupane-type triterpene with a number of biological activities already reported. While potent anti-HIV and antitumoral activities were attributed to BA, it is considered to have a moderate anti-inflammatory activity. Here we evaluated the effects of BA in a mouse model of endotoxic shock. Endotoxemia was induced through intraperitoneally LPS administration, nitric oxide (NO) and cytokines were assessed by Griess method and ELISA, respectively. Treatment of BALB/c mice with BA at 67 mg/kg caused a 100% survival against a lethal dose of lipopolysaccharide (LPS). BA treatment caused a reduction in TNF-α production induced by LPS but did not alter IL-6 production. Moreover, BA treatment increased significantly the serum levels of IL-10 compared to vehicle-treated, LPS-challenged mice. To investigate the role of IL-10 in BA-induced protection, wild-type and IL-10(-/-) mice were studied. In contrast to the observations in IL-10(+/+) mice, BA did not protect IL-10(-/-) mice against a lethal LPS challenge. Addition of BA inhibited the production of pro-inflammatory mediators by macrophages stimulated with LPS, while promoting a significant increase in IL-10 production. BA-treated peritoneal exudate macrophages produced lower concentrations of TNF-α and NO and higher concentrations of IL-10 upon LPS stimulation. Similarly, macrophages obtained from BA-treated mice produced less pro-inflammatory mediators and increased IL-10 when compared to non-stimulated macrophages obtained from vehicle-treated mice. In conclusion, we have shown that BA has a potent anti-inflammatory activity in vivo, protecting mice against LPS by modulating TNF-α production by macrophages in vivo through a mechanism dependent on IL-10.

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Section: Discussionsupporting

confidence: 64%

Potent anti-inflammatory activity of betulinic acid treatment in a model of lethal endotoxemia

Costa

Barbosa-Filho

Maia

et al. 2014

International Immunopharmacology

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“…Our in vitro studies suggested that unlike other tissue MA, splenic MA in inflammation may not release PGE 2 in proportion to increased COX-2 expression [21]. Furthermore, endogenous IL-10, an immunosuppressive cytokine reported to inhibit COX-2 expression in bone marrow MA, peritoneal MA, neutrophils, and cancer cells [22,23], did not significantly modify COX-2 expression by these in vitro splenic MA [21].…”

Section: Introductionmentioning

confidence: 74%

Heat-killed BCG induces biphasic cyclooxygenase 2+ splenic macrophage formation—role of IL-10 and bone marrow precursors

Shibata

Gabbard

Yamashita

et al. 2006

Journal of Leukocyte Biology

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Previous studies have shown that prostaglandin E(2) (PGE(2)) release by splenic F4/80(+) cyclooxygenase (COX)-2(+) macrophages (MØ) isolated from mice, treated with mycobacterial components, plays a major role in the regulation of immune responses. However, splenic MØ, isolated from untreated mice and treated in vitro with lipopolysaccharide and interferon-gamma, express COX-1 and COX-2 within 1 day but release only minimal amounts of PGE(2) following elicitation with calcium ionophore A23187. For further characterization of in vivo requirements for development of PGE(2)-releasing MØ (PGE(2)-MØ), C57Bl/6 [wild-type (WT)], and interleukin (IL)-10-deficient (IL-10(-/-)) mice were treated intraperitoneally with heat-killed Mycobacterium bovis bacillus Calmette-Guerin (HK-BCG). One day following injection, COX-2 was induced in splenic MØ of both mouse strains. However, PGE(2) biosynthesis by these MØ was not increased. Thus, expression of COX-2 is not sufficient to induce PGE(2) production in vivo or in vitro. In sharp contrast, 14 days after HK-BCG treatment, PGE(2) release by COX-2(+) splenic MØ increased as much as sevenfold, and a greater increase was seen in IL-10(-/-) cells than in WT cells. To further determine whether the 14-day splenic PGE(2)-MØ could be derived from bone marrow precursors, we established a chimera in which bone marrow cells were transfused from green fluorescent protein (GFP)-transgenic donors to WT mice. Donors and recipients were treated with HK-BCG simultaneously, and marrow transfusion was performed on Days 1 and 2. On Day 14 after BCG treatment, a significant number of spleen cells coexpressed COX-2 and GFP, indicating that bone marrow-derived COX-2(+) MØ may be responsible for the increased PGE(2) production.

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“…The important direct downstream targets of Stat‐3 are not yet clearly defined, although an additional signal, mediated by the carboxy‐terminal region of the IL‐10R1, is required for the antiinflammatory effects of IL‐10 signaling (44). Antiinflammatory targets include the down‐regulation of a variety of cytokines, chemokines, and inflammatory molecules, including IL‐1, IL‐6, and TNFα, as well as COX‐2 in macrophages (17, 45–48). The IL‐10 effect on these target molecules involves decreased transcription, as well as increased catabolism of the transcripts (47–50).…”

Section: Discussionmentioning

confidence: 99%

Viral interleukin‐10 gene inhibition of inflammation, osteoclastogenesis, and bone resorption in response to titanium particles

Carmody¹,

Schwarz²,

Puzas³

et al. 2002

Arthritis & Rheumatism

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Objective. To evaluate the potential of viral interleukin-10 (vIL-10) gene therapy as an approach to prevent wear debris-induced inflammation, osteoclastogenesis, and bone resorption as it relates to periprosthetic osteolysis in patients with total joint replacements.Methods. Replication-defective adenovirus vectors expressing vIL-10 (AdvIL-10) or LacZ (AdLacZ) target genes were used to transduce fibroblast-like synoviocytes (FLS) in vitro, and the effects of these cells on wear debris-induced proinflammatory cytokine production and receptor activator of nuclear factor B ligand ؉ macrophage colony-stimulating factor splenocyte osteoclastogenesis were assessed by enzyme-linked immunosorbent assay and tartrate-resistant acid phosphatase assay. The effects of AdvIL-10 administration on wear debris-induced osteolysis in vivo were analyzed using the mouse calvaria model, in which AdLacZ was used as the control.Results. In the presence of AdLacZ-infected FLS, titanium particle-stimulated macrophages exhibited a marked increase in secretion of tumor necrosis factor ␣ (TNF␣) (6.5-fold), IL-6 (13-fold), and IL-1 (5-fold). Coculture with AdvIL-10-transduced FLS suppressed cytokine secretion to basal levels, while addition of an anti-IL-10 neutralizing antibody completely blocked this effect. The vIL-10-transduced FLS also inhibited osteoclastogenesis 10-fold in an anti-IL-10-sensitive manner. In vivo, titanium implantation resulted in a 2-fold increase in osteoclasts (P < 0.05) and in a 2-fold increase in sagittal suture area (P < 0.05). This increase over control levels was completely blocked in mice receiving intraperitoneal injections of AdvIL-10, all of whom had measurable serum vIL-10 levels for the duration of the experiment. Immunohistochemistry demonstrated reduced cyclooxygenase 2 and TNF␣ expression in AdvIL-10-infected animals.Conclusion. This study demonstrates that gene delivery of vIL-10 inhibits 3 processes critically involved in periprosthetic osteolysis: 1) wear debris-induced proinflammatory cytokine production, 2) osteoclastogenesis, and 3) osteolysis.

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Inhibition by interleukin-10 of inducible cyclooxygenase expression in lipopolysaccharide-stimulated monocytes: its underlying mechanism in comparison with interleukin-4

Cited by 94 publications

References 43 publications

Potent anti-inflammatory activity of betulinic acid treatment in a model of lethal endotoxemia

Potent anti-inflammatory activity of betulinic acid treatment in a model of lethal endotoxemia

Heat-killed BCG induces biphasic cyclooxygenase 2+ splenic macrophage formation—role of IL-10 and bone marrow precursors

Viral interleukin‐10 gene inhibition of inflammation, osteoclastogenesis, and bone resorption in response to titanium particles

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