Induction of macrophage TNFα, IL-1, IL-6, and PGE2 production by DTH-initiating factors

Ferreri, Nicholas R.; Millet, Isabelle; Paliwal, Vipin; Herzog, W R; Solomon, David H.; Ramabhadran, Rajani; Askenase, Philip W.

doi:10.1016/0008-8749(91)90088-s

Cited by 20 publications

(13 citation statements)

References 36 publications

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“…[39][40][41][42][43][44] This cascade of proinflammatory mediators (as well as chemokines) will directly act on immature, sentinel DCs present in or near inflamed tissues, thus facilitating the up-regulation of CCR7 on their surface and migration into draining lymphoid tissues. [1][2][3][4] The present study demonstrates that the same proinflammatory mediators released at sites of inflammation synergistically induce phenotypic maturation of immature MoDCs to a similar degree as complete pathogens or cellular activation signals such as CD40L.…”

Section: Discussionmentioning

confidence: 99%

Functionally distinct dendritic cell (DC) populations induced by physiologic stimuli: prostaglandin E2 regulates the migratory capacity of specific DC subsets

Luft

Jefford

Luetjens

et al. 2002

Blood

324

333

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Migration of antigen (Ag)-loaded dendritic cells (DCs) from sites of infection into draining lymphoid tissues is fundamental to the priming of T-cell immune responses. We evaluated monocyte-derived DCs (MoDCs) and peripheral blood DCs (PBDCs) to respond to proinflammatory mediators, CD40L, and intact bacteria. All classes of stimuli induced DC phenotypic maturation. However, for MoDCs, only prostaglandin E 2 (PGE 2 )-containing stimuli induced migratory-type DCs. Thus, immature MoDCs that encountered proinflammatory cytokines or CD40L or intact bacteria in the presence of PGE 2 acquired migratory capacity but secreted low levels of cytokines. Conversely, MoDCs that encountered pathogens or CD40L alone become nonmigratory cytokine-secreting cells (proinflammatory type). Interestingly, both migratoryand proinflammatory-type DCs expressed equivalent levels of chemokine receptors, suggesting that the role of PGE 2 was to switch on migratory function. We demonstrate that PGE 2 induces migration via the E-prostanoid 2/E-prostanoid 4 (EP 2 /EP 4 ) receptors and the cAMP pathway. Finally, migratory-type MoDCs stimulated T-cell proliferation and predominantly IL-2 secretion, whereas proinflammatory-type MoDCs induced IFN-␥ production. In contrast, CD1b/c ؉ PBDC rapidly acquired migratory capacity irrespective of the class of stimulus encountered and secreted low levels of cytokines. This suggests that not all mature stages of DCs are destined to migrate to lymphoid organs and that the sequence in which stimuli are encountered significantly affects which functions are expressed. Thus, certain immature DC subsets recruited from the resting precursor pool may have multiple functional fates that play distinct roles during the induction and effector phases of the immune response. These findings have important implications for the clinical utility

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Section: Discussionmentioning

confidence: 99%

Functionally distinct dendritic cell (DC) populations induced by physiologic stimuli: prostaglandin E2 regulates the migratory capacity of specific DC subsets

Luft

Jefford

Luetjens

et al. 2002

Blood

324

333

View full text Add to dashboard Cite

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“…This corresponds to the prior studies that T cell-derived IFNγ activates macrophages, resulting in the production of IL-1β, and macrophage-derived IL-1β is involved in T cell sensitization, inducing IFNγ production. [25][26][27] Our results show that HTN inhibited the expression of IFNγ/IL-22 and IL-1β mRNA in a dose-dependent manner, suggesting an inactivation of T cells by HTN, followed by the inhibition of soluble osteoclast-activating factors (i.e., IL-1β) in the splenocyte and monocyte co-culture system. These data provide an indication that HTN can effectively reduce osteoclast differentiation in the face of high levels of IFNγ produced by T cells, thereby directly or indirectly via decreasing RANKL in osteoblasts.…”

Section: Discussionmentioning

confidence: 60%

Diarylheptanoid Hirsutenone Attenuates Osteoclastogenesis by Suppressing IFNγ and NF-κB Signaling in Th1 and Preosteoclastic Cells

Lee

Jang

Park

et al. 2017

Biological & Pharmaceutical Bulletin

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The aim of the present study was to examine the inhibitory roles and mechanisms of hirsutenone (HTN) in the regulation of osteoclastogenesis. Gene levels were compared to assure the effects of HTN on osteoclastogenesis in mouse splenocytes/CD4 T cells, mouse macrophage-like cell line RAW264.7 (preosteoclast), MG63 (osteoblast), and RPMI1788 (B cell) cells. The mechanism by which HTN regulates the degradation of tumor necrosis factor receptor-associated factor 6 (TRAF6) and inhibits inhibitor of kappaB (IκB) and nuclear factor-kappaB (NF-κB) signaling was examined by Western blotting and luciferase reporter assays. Our results demonstrated that HTN effectively downregulated the expression of interferon γ (IFNγ), interleukin-22 (IL-22), IL-1β, and tartrate-resistant acid phosphatase (TRAP) in splenocyte-/CD4 -RAW264.7 co-culture system. Moreover, receptor activator of nuclear factor-κB ligand (RANKL) and CD25 expression were also significantly inhibited in MG63 and CD4 single culture system, suggesting an additional independent effect of HTN on osteoclastogenesis. Notably, TRAF6 was markedly degraded along with a decrease in nuclear factor of activated T-cells (NFATc) and NF-κB activities in RAW264.7 cells. Finally, we concluded that HTN directly or indirectly inhibits osteoclastogenesis via the inhibition of NF-κB signaling by promoting TRAF6 degradation, and plays a crucial role in suppressing the expression of RANKL and cytokines expressed in IFNγ-producing T-helper 1 (Th1) cells. These findings suggest that HTN may be a promising therapeutic candidate for diseases resulting from bone loss.Key words osteoclastogenesis; hirsutenone; interferon γ; receptor activator of nuclear factor-κB ligand; tumor necrosis factor receptor-associated factor 6 Bone serves as an ion reservoir for the body, as well as the location of several specialized bone cells, such as osteoblasts, osteocytes, and osteoclasts, which reside within this complex tissue.1,2) Bone loss, which may induce an imbalance between bone formation and resorption, as a result of aging and after menopause, can lead to osteoporosis, which is characterized by reduced bone mass, deterioration of bone architecture, and an increased risk of fatal bone fractures.3,4) Osteoclasts (OC), the bone-resorbing cells generated from the same precursors as monocyte/macrophages, crosstalk with activated T cells to form activated osteoclasts directly by producing interleukin-7 (IL-7) and receptor activator of nuclear factor-κB ligand (RANKL), and indirectly by promoting the production of RANKL by osteoblasts and fibroblasts via the production of pro-inflammatory cytokines (i.e., IL-1, -6, -17, and interferon (IFN)-γ).5,6) Of these, interleukin-1β (IL-1β), one of the most well-known proinflammatory cytokines, has been reported as an effective stimulator of bone resorption through the upregulation of RANKL.7) In addition, IL-22 produced by activated T cells has been shown to promote osteoclastogenesis, leading to bone erosion in rheumatoid arthritis. 8)As the binding of RANKL to...

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“…From these findings, we hypothesize that the decline in telomerase activity in tumors treated with indomethacin in vivo involves the following mechanisms: a decrease of vascular permeability by inhibition of the local production of prostaglandin E 2 , which is generated in tumors and in inflammatory cells, 31,32) leading to suppression of tumor growth through a decrease of nutrition; secondly, an enhancement of immune response via inhibition of increased formation of immunosuppressing prostaglandin E 2 .…”

Section: Discussionmentioning

confidence: 98%

Indomethacin Suppresses the Growth of Colon 26, Meth‐A and FM3A Tumors in Mice by Reducing the Prostaglandin E₂ Content and Telomerase Activity in Tumor Tissues

Ogino

Higuchi

Murata³

et al. 1999

Japanese Journal of Cancer Research

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The antitumor effect of indomethacin on Colon 26, Meth-A and FM3A tumors was investigated in mice. The prostaglandin E 2 content in tumor tissues was assayed to find out if indomethacin acts on tumors, and the telomerase activity in tumors and somatic tissues (testis, liver, spleen and colon) was also monitored during indomethacin treatment. Growth of Colon 26, Meth-A and FM3A tumors was significantly (P< < < <0.001-0.05) suppressed by indomethacin compared to the untreated controls. The prostaglandin E 2 content in the three tumors was markedly (P< < < <0.001) reduced by indomethacin. Telomerase activity in Colon 26 and FM3A tumors was significantly (P< < < <0.001) lower than that of untreated tumors (80% and 45% decrease versus the controls, respectively), and the activity in Meth-A tumor was slightly decreased (10% decrease versus the control) by indomethacin. Telomerase activity in the somatic tissues was not significantly affected by indomethacin. In summary, this study shows the effectiveness of indomethacin as an antitumor agent against three types of tumors, and suggests that indomethacin affects telomerase activity in tumors in vivo.Key words: Indomethacin -Prostaglandin E 2 -Telomerase activity -Fluorescence-based telomeric repeat amplification protocolThe antitumor effect of indomethacin on tumors in cancer patients 1, 2) and in animals 3, 4) has been described. We previously showed that indomethacin suppresses the growth of Colon 26 tumor in mice by enhancing the cellular immune function and improving cancer cachexia. 5)Indomethacin does not have a cytotoxic effect on Colon 26 tumor cells in vitro, 5) but it may have an antitumor effect via immunological pathways. We previously reported that indomethacin treatment of tumors reduces tumor size less in nude mice (deficient in T-lymphocytes) than in normal mice, compared with untreated tumors. 6)Although these results indicate that the effectiveness of indomethacin as an antitumor agent is, at least in part, due to its modification of T-cell-mediated immune functions, the precise mechanism of tumor growth suppression by indomethacin remains unknown.Recent studies have shown that many proliferating tumor cells retain a certain level of telomerase activity. [7][8][9] We previously reported that tumor growth in Colon 26-bearing mice is significantly suppressed by indomethacin treatment compared with the untreated controls, and that the telomerase activity declines preferentially in tumor tissues, while telomerase activity in somatic tissues is not significantly affected by indomethacin treatment.10) More recently, Kido et al. 11) reported that tumor size reduction by cisplatin treatment correlates with a decline in telomerase activity in tumor tissues.In this study, we transplanted Colon 26, Meth-A and FM3A tumors into normal mice to assess if the effect of indomethacin is independent of tumor cell type. Prostaglandin E 2 synthesis is inhibited by indomethacin, and therefore we measured the prostaglandin E 2 content in tumors to confirm the effect of ind...

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Induction of macrophage TNFα, IL-1, IL-6, and PGE2 production by DTH-initiating factors

Cited by 20 publications

References 36 publications

Functionally distinct dendritic cell (DC) populations induced by physiologic stimuli: prostaglandin E2 regulates the migratory capacity of specific DC subsets

Functionally distinct dendritic cell (DC) populations induced by physiologic stimuli: prostaglandin E2 regulates the migratory capacity of specific DC subsets

Diarylheptanoid Hirsutenone Attenuates Osteoclastogenesis by Suppressing IFNγ and NF-κB Signaling in Th1 and Preosteoclastic Cells

Indomethacin Suppresses the Growth of Colon 26, Meth‐A and FM3A Tumors in Mice by Reducing the Prostaglandin E₂ Content and Telomerase Activity in Tumor Tissues

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Induction of macrophage TNFα, IL-1, IL-6, and PGE2 production by DTH-initiating factors

Cited by 20 publications

References 36 publications

Functionally distinct dendritic cell (DC) populations induced by physiologic stimuli: prostaglandin E2 regulates the migratory capacity of specific DC subsets

Functionally distinct dendritic cell (DC) populations induced by physiologic stimuli: prostaglandin E2 regulates the migratory capacity of specific DC subsets

Diarylheptanoid Hirsutenone Attenuates Osteoclastogenesis by Suppressing IFNγ and NF-κB Signaling in Th1 and Preosteoclastic Cells

Indomethacin Suppresses the Growth of Colon 26, Meth‐A and FM3A Tumors in Mice by Reducing the Prostaglandin E2 Content and Telomerase Activity in Tumor Tissues

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Product

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Indomethacin Suppresses the Growth of Colon 26, Meth‐A and FM3A Tumors in Mice by Reducing the Prostaglandin E₂ Content and Telomerase Activity in Tumor Tissues