Innate immune responses of primary murine macrophage-lineage cells and RAW 264.7 cells to ligands of Toll-like receptors 2, 3, and 4

Berghaus, Londa J.; Moore, James N.; Hurley, David J.; Vandenplas, Michel L.; Fortes, Barbara; Wolfert, Margreet A.; Boons, Geert‐Jan

doi:10.1016/j.cimid.2009.07.001

Cited by 132 publications

(120 citation statements)

References 22 publications

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“…However, complementary in vitro and in vivo investigations using primary cells activated by risperidone and haloperidol should be performed in order to confirm the results described here. Although RAW 264.7 cell line displays some phenotypes similar to primary cells, there are some notable differences, including differential gene expression (Berghaus et al 2010). Another limitation of our study stems from a small number of drug concentrations tested here, excluding concentrations similar to those found in plasma.…”

Section: Discussionmentioning

confidence: 67%

Haloperidol and Risperidone at high concentrations activate an in vitro inflammatory response of RAW 264.7 macrophage cells by induction of apoptosis and modification of cytokine levels

et al. 2015

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Antipsychotic drugs, such as haloperidol and risperidone, are used in long-term treatment of psychiatric patients and thus increase the risk of obesity and other metabolic dysfunctions. Available evidence suggests that these drugs have pro-inflammatory effect, which contributes to the establishment of endocrine disturbances. However, results yielded by extant studies are inconsistent. Therefore, in this work, we tested the in vitro effects of different high concentrations of haloperidol and risperidone on the activation of isolated macrophages (RAW 264.7 cell line). The results indicated that macrophages were activated by both drugs. In addition, the activation involved an increase in nitric oxide levels and apoptosis events by modulation of caspases 8 and 3 levels and a decrease of the Bcl-2/BAX gene expression ratio. Cells treated with haloperidol and risperidone also presented higher concentrations of inflammatory cytokines (IL-1β, IL-6, TNFα) and low levels of IL-6 anti-inflammatory cytokine in a dose-dependent manner. Despite the limitation of cell line studies based solely on macrophages cells, we suggest that antipsychotic drugs could potentially exacerbate inflammatory processes in peripheral tissues (blood and fat). The continued activation of macrophages could contribute to the development of obesity and other endocrine disturbances caused by the use of antipsychotic drugs.

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Section: Discussionmentioning

confidence: 67%

Haloperidol and Risperidone at high concentrations activate an in vitro inflammatory response of RAW 264.7 macrophage cells by induction of apoptosis and modification of cytokine levels

et al. 2015

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“…BMMΦ and IC-21 cells continued to up-regulate expression of maturation markers CD14 and F4/80, and CD14 and Fc, respectively (Figure 4 and Table 2), over 21 days, reflecting progressively distinct differentiation state [35, 48, 55]. Another study, also comparing variations between different macrophage sources, identified unique external receptor expression by each macrophage type [40]. However, consistent with our findings, this identified similarly high CD14 expression by BMMΦ and RAW cells compared to the other cell lines compared [40].…”

Section: Discussionmentioning

confidence: 99%

Extended culture of macrophages from different sources and maturation results in a common M2 phenotype

Chamberlain

Holt-Casper

Gonzalez-Juarrero

et al. 2015

J Biomedical Materials Res

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Inflammatory responses to biomaterials heavily influence the environment surrounding implanted devices, often producing foreign body reactions. The macrophage is a key immunomodulatory cell type consistently associated with implanted biomaterials and routinely employed in short term in vitro cell studies of biomaterials aiming to reproduce host responses. Inconsistencies within these studies, including differently sourced cells, different durations of culture, and assessment of different activation markers, lead to many conflicting results in vitro that confound consistency and conclusions. We hypothesize that different experimentally popular monocyte-macrophage cell types have intrinsic in vitro culture-specific differences that yield conflicting results. Recent studies demonstrate changes in cultured macrophage cytokine expression over time, leading to the hypothesis that changes in macrophage phenotype also occur in response to extended culture. Here, macrophage cells of different transformed and primary-derived origins were cultured for 21 days on model polymer biomaterials. Cell type-based differences in morphology and cytokine/chemokine expression as well as changes in cell surface biomarkers associated with differentiation stage, activation state, and adhesion were compared. Results reflect consistent macrophage development towards an M2 phenotype via up-regulation of the macrophage mannose receptor for all cell types following 21-day extended culture. Significantly, implanted biomaterials experiencing the foreign body response and encapsulation in vivo often elicit a shift towards an analogous M2 macrophage phenotype. In vitro “default” of macrophage cultures, regardless of lineage, to this M2 state in the presence of biomaterials at long culture periods is not recognized but has important implications to in vitro modeling of in vivo host response.

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“…MHC I and II mean fluorescent brightness values were also determined as a further check of the purity of each cell type. The gating and assessment of fluorescence was carried out using Accuri analysis software (Accuri Cytometers) as previously described (38).…”

Section: Tlr5 Flow Cytometrymentioning

confidence: 99%

Disparities in TLR5 Expression and Responsiveness to Flagellin in Equine Neutrophils and Mononuclear Phagocytes

Kwon

Gewirtz

Hurley

et al. 2011

The Journal of Immunology

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As sentinel cells of the innate immune system, neutrophils and mononuclear phagocytes use specific TLRs to recognize the conserved molecular patterns that characterize microbes. This study was performed to compare the responses of equine neutrophils and mononuclear phagocytes to LPS and flagellin, components of bacteria that are recognized by TLR4 and TLR5, respectively. Neutrophils and mononuclear phagocytes isolated from healthy horses were incubated in vitro with LPS, flagellin, or pronase-inactivated flagellin in the presence or absence of polymyxin B. Production of reactive oxygen species and expression of mRNA for proinflammatory cytokines were used as readouts for activation of neutrophils; production of TNF-α was used for the mononuclear cells. Western blot analysis and flow cytometry were used to detect TLR5 protein in both cell types. Although the neutrophils responded to both LPS and flagellin by producing reactive oxygen species and expressing mRNA for proinflammatory cytokines, flagellin had no stimulatory effect on monocytes or macrophages. Although both neutrophils and monocytes expressed mRNA for TLR5, it appeared to be translated into protein only by the neutrophils. Incubation with neither LPS nor IFN-γ altered TLR5 expression by the monocytes. These findings indicate that flagellin has disparate effects on neutrophils and mononuclear phagocytes isolated from horses, a species that is exquisitely sensitive to the TLR4 ligand, LPS, and that equine mononuclear phagocytes, unlike corresponding cells of other mammalian species, lack surface expression of TLR5 and do not respond to flagellin.

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Innate immune responses of primary murine macrophage-lineage cells and RAW 264.7 cells to ligands of Toll-like receptors 2, 3, and 4

Cited by 132 publications

References 22 publications

Haloperidol and Risperidone at high concentrations activate an in vitro inflammatory response of RAW 264.7 macrophage cells by induction of apoptosis and modification of cytokine levels

Haloperidol and Risperidone at high concentrations activate an in vitro inflammatory response of RAW 264.7 macrophage cells by induction of apoptosis and modification of cytokine levels

Extended culture of macrophages from different sources and maturation results in a common M2 phenotype

Disparities in TLR5 Expression and Responsiveness to Flagellin in Equine Neutrophils and Mononuclear Phagocytes

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