Macrophages in Inflammatory Bowel Disease (IBD)
Macrophage Biology in IBD Pathogenic Role of Macrophages in IBD Therapies of Targeting Macrophages in IBD Related Services Related Products Scientific Resources
IBD is an inflammatory disorder of the colon and small intestine. The pathogenesis of IBD is correlated with alterations in the immunological mechanisms involved in the resolution of inflammation resulting in excessive and persistent inflammation. More recently, specific mechanisms involved in the resolution of inflammation have been identified with macrophages playing a key part in preventing an excessive immune response. Intestinal macrophages are considered to be the main players in establishing and maintaining gut homeostasis. Deregulation of intestinal macrophages, therefore, results in a loss of tolerance towards commensal bacteria and food antigens, which is believed to underlie the chronic inflammation observed in IBD.
Macrophage Biology in IBD
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Factors
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Impact on Macrophage Phenotype
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Cytokine Milieu
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The cytokine-rich environment of the inflamed gut skews macrophage polarization.
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High levels of IFN-γ and LPS favor M1 polarization.
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IL-10 and TGF-β secretion by regulatory T cells (Tregs) and epithelial cells promote M2 polarization.
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Hypoxia
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Hypoxia-inducible factors (HIFs) modulate macrophage metabolism and function, favoring a pro-inflammatory phenotype under certain conditions.
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Dietary and Microbial Metabolites
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Short-chain fatty acids (SCFAs) such as butyrate, derived from microbial fermentation, promote M2-like anti-inflammatory activity.
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Metabolites like succinate can drive M1 polarization by activating pro-inflammatory pathways.
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Extracellular Matrix Components
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Changes in the extracellular matrix, such as increased deposition of fibronectin or hyaluronan during inflammation, provide signals that can exacerbate M1 polarization and perpetuate inflammation.
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In IBD, an imbalance between M1 and M2 macrophages is frequently observed, and overexpression of M1 macrophages exacerbates disease pathology. The intestinal microenvironment has a profound effect on macrophage behavior, shaping macrophage phenotype and function through a range of signals from the extracellular matrix, stromal cells, cytokines, and metabolites. Key factors include:
Macrophages do not act in isolation. Their interactions with intestinal epithelial cells and the gut microbiota are central to maintaining intestinal homeostasis and mediating inflammatory responses in IBD.
Macrophage-Epithelial Cell Interactions
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Macrophages support epithelial integrity by secreting growth factors, which promote epithelial cell proliferation and repair.
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Macrophages respond to epithelial cell-derived alarmins (e.g., IL-33, HMGB1) by amplifying inflammatory signaling.
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Intestinal macrophages, located beneath the epithelium, sample luminal antigens and convey signals to both epithelial and immune cells.
Macrophage-Microbiota Interactions
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Macrophages detect microbial components through pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) and NOD-like receptors (NLRs).
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Microbiota-derived metabolites influence macrophage metabolism, directly impacting their inflammatory or anti-inflammatory functions.
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A healthy microbiota promotes tolerogenic macrophage phenotypes, while dysbiosis skews macrophages toward a pro-inflammatory state.
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Macrophages shape the composition of the gut microbiota through the secretion of antimicrobial peptides and cytokines.
Pathogenic Role of Macrophages in IBD
Macrophage-Driven Cytokine Storms
Tumor Necrosis Factor-Alpha (TNF-α)
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Activating NF-κB pathways in epithelial cells and immune cells.
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Promoting recruitment of neutrophils and lymphocytes to the inflamed mucosa.
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Inducing apoptosis in intestinal epithelial cells, exacerbating mucosal damage.
Interleukin-1 Beta (IL-1β)
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Drives the differentiation of naïve T cells into pro-inflammatory Th17 subsets.
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Enhances vascular permeability, worsening local tissue edema.
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Potentiates fibroblast activation, laying the groundwork for fibrosis.
Interleukin-6 (IL-6)
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Inducing the survival and proliferation of effector T cells, particularly Th17 and Tfh cells.
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Disrupting mucosal homeostasis through STAT3-mediated epithelial cell dysregulation.
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Supporting the generation of acute-phase reactants, further escalating systemic inflammatory responses.
Contribution to Intestinal Barrier Dysfunction
Secretion of Barrier-Disrupting Cytokines
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TNF-α and IL-1β induce disassembly of tight junction proteins, such as occludin and claudin, increasing epithelial permeability.
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IL-6 disrupts epithelial regeneration by impairing stem cell niches in the crypts.
Impaired Clearance of Apoptotic Cells
Macrophages exhibit defective efferocytosis in IBD, resulting in the accumulation of apoptotic epithelial cells. This unregulated cell death fosters breaches in the barrier and exposes underlying tissues to luminal antigens.
Stimulation of Mucosal Immune Responses
Increased epithelial permeability allows the translocation of microbial products, such as lipopolysaccharides (LPS), into the lamina propria. These products engage macrophage Toll-like receptors (TLRs), perpetuating a vicious cycle of immune activation and tissue injury.
Therapies of Targeting Macrophages in IBD
The pathogenesis of IBD is multifactorial, involving genetic, environmental, microbial, and immunological contributors. Among these, macrophages have emerged as pivotal players in driving intestinal inflammation, presenting a unique therapeutic target for addressing the complex mechanisms underlying IBD.
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Strategies
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Specific Programs
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Modulating Macrophage Polarization
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Small molecules: Agents such as Tofacitinib (a JAK inhibitor) reduce M1-driven cytokine signaling, indirectly promoting M2-like activity.
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Cytokine therapies: IL-10 and IL-4 administration has shown promise in preclinical models for promoting anti-inflammatory macrophage phenotypes.
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Targeting Macrophage Recruitment and Trafficking
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Inhibition of inflammatory macrophage recruitment into the inflamed mucosa by Natalizumab, vedolizumab, and other compounds in development.
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Integrin blockers: Therapies targeting integrins (e.g., Vedolizumab) reduce macrophage trafficking by interfering with leukocyte adhesion molecules.
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Macrophage-specific Nanomedicine
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Macrophage-targeted nanoparticles: Mannosylated or folic acid conjugated liposomes promote differentiation of CD206+ or folate receptor-positive (FR+) inflammatory myeloid cells into pro-resolving macrophages.
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Inhibiting Macrophage Cytokine Production
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Corticosteroids inhibit nuclear factor-κB (NF-κB) and activator protein 1, thereby blocking pro-inflammatory gene transcription.
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Azathioprine and 6-mercaptopurine inhibit Ras-related C3 botulinum toxin substrate 1 (Rac1) activity, preventing JUN N-terminal kinase (JNK) phosphorylation.
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Methotrexate reduces pro-inflammatory cytokine production only in TS+ inflammatory macrophages.
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Enhancing Macrophage-mediated Resolution of Inflammation
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Specialized pro-resolving mediators (SPMs): These lipid mediators (e.g., resolvins, protectins) enhance macrophage phagocytosis of apoptotic cells and debris, accelerating tissue healing.
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Macrophage adoptive transfer: Infusion of ex vivo-modified anti-inflammatory macrophages is being investigated as a potential therapeutic modality.
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Related Services
Based on a powerful macrophage therapeutics development platform, Creative Biolabs offers extremely useful and valuable biotechnological services for macrophage development projects. Our featured services include but are not limited to:
Macrophage Isolation and Culture Service Macrophage Polarization Assay Macrophage Phenotype Identification Service Macrophage Characterization Service Macrophage Reprogramming Service Macrophage Engineering Service for Drug Delivery Macrophage Marker Development Service
Creative Biolabs has built a highly experienced team of scientists and quality staff that have a long history in macrophage isolation and culture. Human monocytes, human alveolar, murine peritoneal cavity, murine bone marrow, murine lung, and murine adipose tissues are available for macrophage isolation and culture.
In this assay, except for different macrophage polarization by adding certain stimuli, we also provide support for our clients with verification of each polarized macrophage-based on the distinctly expressed surface markers and/or produced cytokines.
Creative Biolabs has established a cutting-edge platform for macrophage development. A full range of macrophage markers, including multiple cell surface markers, transcription factors, and cytokine profiles, are available for the identification of M1 and M2 macrophages.
Creative Biolabs provides a full portfolio of high-quality macrophage characterization services, which focus on the difference analysis in morphology, phenotype, proliferation capability, phagocytosis capability, antigen presentation capability, and cytokine expression profile.
Our seasoned scientists have developed several efficient strategies for macrophage reprogramming, including employing gene regulatory networks, nanoparticles, microRNA and in vivo Lentivirus-based macrophage reprogramming services.
As a leading specialist in engineering macrophages, Creative Biolabs provides comprehensive R&D services of engineering M1 macrophages, macrophage-derived exosomes, and macrophage membranes as drug carriers.
Creative Biolabs has developed several transcriptome-based approaches for the identification of novel macrophage markers. Macrophage-specific markers and M1/M2 macrophage-specific markers can be identified effectively through this high-throughput system.
Related Products
Creative Biolabs designs and develops a range of useful products to aid our customers' macrophage research in IBD.
You can browse below and click to learn more.
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Cat.No
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Product Name
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Product Type
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MTS-0922-JF10
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Human Macrophages, Alveolar
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Human Macrophages
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MTS-0922-JF99
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Human M0 Macrophages, 1.5 x 10^6
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Human M0 Macrophages
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MTS-0922-JF52
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C57/129 Mouse Macrophages, Bone Marrow
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C57/129 Mouse Macrophages
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MTS-0922-JF7
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Human M2 Macrophages, Peripheral Blood, 10 x 10^6
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Human M2 Macrophages
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MTS-1022-JF1
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B129 Mouse Bone Marrow Monocytes, 1 x 10^7 cells
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Immune cells
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MTS-1022-JF10
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Human PB CD14+ Monocytes (Age: 23), 5 x 10^7 cells
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Immune cells
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MTS-1022-JF5
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CD1 Mouse Bone Marrow Monocytes, 1 x 10^7 cells
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Immune cells
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MTS-1123-HM11
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Monocyte To Macrophage Differentiation Associated Protein (MMA) ELISA Kit, Colorimetric
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ELISA Kit
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MTS-1123-HM9
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Macrophage Expressed Gene 1 (MPEG1) ELISA Kit, Colorimetric
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ELISA Kit
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MTS-1123-HM15
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Macrophage Chemokine Ligand 19 (CCL19) ELISA Kit, qPCR
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ELISA Kit
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MTS-1123-HM50
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Macrophage Migration Inhibitory Factor (MIF) Competition ELISA Kit
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ELISA Kit
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MTS-1122-YF49
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MacroCargo™ Human Monocyte-derived Macrophages (MDMs) with Chemo drugs (Nanoparticle System, Oligomannose-coated liposome)
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MacroCargo
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MTS-1122-YF19
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MacroCargo™ Human PBMC-derived Macrophages with Chemo drugs (Nanoparticle System, PLGA)
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MacroCargo
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MTS-1122-YF49
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MacroCargo™ Human Monocyte-derived Macrophages (MDMs) with Chemo drugs (Nanoparticle System, Oligomannose-coated liposome)
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MacroCargo
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MTS-0124-LX2
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IFN-α Lentiviral Particle for Macrophage Engineering
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Virus Particles
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MTS-0124-LX3
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IL-1β Lentiviral Particle for Macrophage Engineering
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Virus Particles
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Scientific Resources
