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Papers by Muhammad Sohel Mia

Research paper thumbnail of Myeloid cells in autoimmune diseases

Research paper thumbnail of FINAL revised Text-Zhang-131202

Research paper thumbnail of ApoE Production in Human Monocytes and Its Regulation by Inflammatory Cytokines

PLoS ONE, 2013

The apoE production by tissue macrophages is crucial for the prevention of atherosclerosis and th... more The apoE production by tissue macrophages is crucial for the prevention of atherosclerosis and the aim of this study was to further elucidate how this apolipoprotein is regulated by cytokines present during inflammation. Here we studied apoE production in peripheral blood mononuclear cells (PBMC) and analysis was made with a newly developed apoE ELISpot assay. In PBMC, apoE secretion was restricted to monocytes with classical (CD14 ++ CD16 2) and intermediate (CD14 + CD16 +) monocytes being the main producers. As earlier described for macrophages, production was strongly upregulated by TGF-b and downregulated by bacterial lipopolysaccharide (LPS) and the inflammatory cytokines IFN-c, TNF-a and IL-1b. We could here show that a similar down-regulatory effect was also observed with the type I interferon, IFN-a, while IL-6, often regarded as one of the more prominent inflammatory cytokines, did not affect TGF-b-induced apoE production. The TNF-a inhibitor Enbrel could partly block the down-regulatory effect of IFN-c, IFN-a and IL-1b, indicating that inhibition of apoE by these cytokines may be dependent on or synergize with TNF-a. Other cytokines tested, IL-2, IL-4, IL-12, IL-13, IL-17A and IL-23, had no inhibitory effect on apoE production. In contrast to the effect on monocytes, apoE production by primary hepatocytes and the hepatoma cell line HepG2 was more or less unaffected by treatment with cytokines or LPS.

Research paper thumbnail of Adoptive transfer of cytokine-induced immunomodulatory adult microglia attenuates experimental autoimmune encephalomyelitis in DBA/1 mice

Glia, 2014

Microglia are resident antigen-presenting cells in the central nervous system (CNS) that either s... more Microglia are resident antigen-presenting cells in the central nervous system (CNS) that either suppress or promote disease depending on their activation phenotype and the microenvironment. Multiple sclerosis (MS) is a chronic inflammatory disease causing demyelination and nerve loss in the CNS, and experimental autoimmune encephalomyelitis (EAE) is an animal model of MS that is widely used to investigate pathogenic mechanisms and therapeutic effects. We isolated and cultured microglia from adult mouse brains and exposed them to specific combinations of stimulatory molecules and cytokines, the combination of IL-4, IL-10, and TGF-b yielding the optimal regime for induction of an immunosuppressive phenotype (M2). M2 microglia were characterized by decreased expression or production of CD86, PD-L1, nitric oxide, and IL-6, increased expression of PD-L2, and having a potent capacity to retain their phenotype on secondary proinflammatory stimulation. M2 microglia induced regulatory T cells, suppressed T-cell proliferation, and downmodulated M1-associated receptor expression in M1 macrophages. Myelin oligodendrocyte glycoprotein (MOG)-induced EAE was induced in DBA/1 mice and at different time points (0, 5, 12, or 15 days postimmunization) 3 3 10 5 M2 microglia were transferred intranasally. A single transfer of M2 microglia attenuated the severity of established EAE, which was particularly obvious when the cells were injected at 15 days postimmunization. M2 microglia-treated mice had reduced inflammatory responses and less demyelination in the CNS. Our findings demonstrate that adult M2 microglia therapy represents a novel intervention that alleviated established EAE and that this therapeutic principle may have relevance for treatment of MS patients.

Research paper thumbnail of Knowledge, attitude and practice regarding breast cancer among health professionals

European Journal of Cancer, 2002

Research paper thumbnail of Adoptive Transfer of Immunomodulatory M2 Macrophages Prevents Type 1 Diabetes in NOD Mice

Research paper thumbnail of An optimized Protocol for Human M2 Macrophages using M-CSF and IL-4/IL-10/TGF-β Yields a Dominant Immunosuppressive Phenotype

Scand. J. Immunol., 2014

Monocytes are highly abundant circulatory effector cells and play a vital role in driving or reso... more Monocytes are highly abundant circulatory effector cells and play a vital role in driving or resolving inflammatory processes depending on their activation phenotype. We investigated and compared a panel of polarization protocols of blood-derived monocytes to achieve a stable, optimal and effective regimen for in vitro induction of immunosuppressive human macrophages, evaluating their surface receptor expression, cytokine profile, scavenging function and ability to suppress T-cell proliferation. Importantly, we assessed the effect of copolarization or secondary pro-inflammatory stimulation of a primary anti-inflammatory activation phenotype. A combination of IL-4/IL-10/TGF-b yielded a relatively stable and dominant immunosuppressive phenotype characterized by higher IL-10 production and down-regulated TNF-a, IL-6, CD86, CD274 and MHC II expression. Functionally, IL-4/IL-10/TGF-b-stimulated macrophages (M2) had a potent deactivating effect on a subsequent pro-inflammatory LPS/IFNc-activated macrophage (M1) stimulation and significantly suppressed T-cell proliferation. Monocytes derived from patients with chronic inflammatory diseases could be induced to be anti-inflammatory using this protocol. Pre-differentiation with GM-CSF or M-CSF was further demonstrated to enhance final M1/M2 activation status. Our findings indicate a robust polarization protocol for generation of specific immunosuppressive human monocyte-derived macrophages.

Research paper thumbnail of Myeloid cells in autoimmune diseases

Research paper thumbnail of FINAL revised Text-Zhang-131202

Research paper thumbnail of ApoE Production in Human Monocytes and Its Regulation by Inflammatory Cytokines

PLoS ONE, 2013

The apoE production by tissue macrophages is crucial for the prevention of atherosclerosis and th... more The apoE production by tissue macrophages is crucial for the prevention of atherosclerosis and the aim of this study was to further elucidate how this apolipoprotein is regulated by cytokines present during inflammation. Here we studied apoE production in peripheral blood mononuclear cells (PBMC) and analysis was made with a newly developed apoE ELISpot assay. In PBMC, apoE secretion was restricted to monocytes with classical (CD14 ++ CD16 2) and intermediate (CD14 + CD16 +) monocytes being the main producers. As earlier described for macrophages, production was strongly upregulated by TGF-b and downregulated by bacterial lipopolysaccharide (LPS) and the inflammatory cytokines IFN-c, TNF-a and IL-1b. We could here show that a similar down-regulatory effect was also observed with the type I interferon, IFN-a, while IL-6, often regarded as one of the more prominent inflammatory cytokines, did not affect TGF-b-induced apoE production. The TNF-a inhibitor Enbrel could partly block the down-regulatory effect of IFN-c, IFN-a and IL-1b, indicating that inhibition of apoE by these cytokines may be dependent on or synergize with TNF-a. Other cytokines tested, IL-2, IL-4, IL-12, IL-13, IL-17A and IL-23, had no inhibitory effect on apoE production. In contrast to the effect on monocytes, apoE production by primary hepatocytes and the hepatoma cell line HepG2 was more or less unaffected by treatment with cytokines or LPS.

Research paper thumbnail of Adoptive transfer of cytokine-induced immunomodulatory adult microglia attenuates experimental autoimmune encephalomyelitis in DBA/1 mice

Glia, 2014

Microglia are resident antigen-presenting cells in the central nervous system (CNS) that either s... more Microglia are resident antigen-presenting cells in the central nervous system (CNS) that either suppress or promote disease depending on their activation phenotype and the microenvironment. Multiple sclerosis (MS) is a chronic inflammatory disease causing demyelination and nerve loss in the CNS, and experimental autoimmune encephalomyelitis (EAE) is an animal model of MS that is widely used to investigate pathogenic mechanisms and therapeutic effects. We isolated and cultured microglia from adult mouse brains and exposed them to specific combinations of stimulatory molecules and cytokines, the combination of IL-4, IL-10, and TGF-b yielding the optimal regime for induction of an immunosuppressive phenotype (M2). M2 microglia were characterized by decreased expression or production of CD86, PD-L1, nitric oxide, and IL-6, increased expression of PD-L2, and having a potent capacity to retain their phenotype on secondary proinflammatory stimulation. M2 microglia induced regulatory T cells, suppressed T-cell proliferation, and downmodulated M1-associated receptor expression in M1 macrophages. Myelin oligodendrocyte glycoprotein (MOG)-induced EAE was induced in DBA/1 mice and at different time points (0, 5, 12, or 15 days postimmunization) 3 3 10 5 M2 microglia were transferred intranasally. A single transfer of M2 microglia attenuated the severity of established EAE, which was particularly obvious when the cells were injected at 15 days postimmunization. M2 microglia-treated mice had reduced inflammatory responses and less demyelination in the CNS. Our findings demonstrate that adult M2 microglia therapy represents a novel intervention that alleviated established EAE and that this therapeutic principle may have relevance for treatment of MS patients.

Research paper thumbnail of Knowledge, attitude and practice regarding breast cancer among health professionals

European Journal of Cancer, 2002

Research paper thumbnail of Adoptive Transfer of Immunomodulatory M2 Macrophages Prevents Type 1 Diabetes in NOD Mice

Research paper thumbnail of An optimized Protocol for Human M2 Macrophages using M-CSF and IL-4/IL-10/TGF-β Yields a Dominant Immunosuppressive Phenotype

Scand. J. Immunol., 2014

Monocytes are highly abundant circulatory effector cells and play a vital role in driving or reso... more Monocytes are highly abundant circulatory effector cells and play a vital role in driving or resolving inflammatory processes depending on their activation phenotype. We investigated and compared a panel of polarization protocols of blood-derived monocytes to achieve a stable, optimal and effective regimen for in vitro induction of immunosuppressive human macrophages, evaluating their surface receptor expression, cytokine profile, scavenging function and ability to suppress T-cell proliferation. Importantly, we assessed the effect of copolarization or secondary pro-inflammatory stimulation of a primary anti-inflammatory activation phenotype. A combination of IL-4/IL-10/TGF-b yielded a relatively stable and dominant immunosuppressive phenotype characterized by higher IL-10 production and down-regulated TNF-a, IL-6, CD86, CD274 and MHC II expression. Functionally, IL-4/IL-10/TGF-b-stimulated macrophages (M2) had a potent deactivating effect on a subsequent pro-inflammatory LPS/IFNc-activated macrophage (M1) stimulation and significantly suppressed T-cell proliferation. Monocytes derived from patients with chronic inflammatory diseases could be induced to be anti-inflammatory using this protocol. Pre-differentiation with GM-CSF or M-CSF was further demonstrated to enhance final M1/M2 activation status. Our findings indicate a robust polarization protocol for generation of specific immunosuppressive human monocyte-derived macrophages.