Immune modulation by Lacto-N-fucopentaose III in experimental autoimmune encephalomyelitis

Zhu, Bing; Trikudanathan, Subbulaxmi; Zozulya, Alla L.; Sandoval-Garcia, Carolina; Kennedy, Jennifer K.; Atochina, Olga; Norberg, Thomas; Castagner, Bastien; Seeberger, Peter H.; Fábry, Zsuzsa; Harn, Donald A.; Khoury, Samia J.; Guleria, Indira

doi:10.1016/j.clim.2011.12.006

Cited by 50 publications

(41 citation statements)

References 46 publications

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“…This model causes inflammation and demyelination similar to the disease manifestation seen in humans (Zhu et al 2011;Markoullis et al 2012). EAE is a T-cell-mediated autoimmune disease of the CNS induced by immunizing animals with myelin antigens.…”

Section: Introductionmentioning

confidence: 77%

Medium-dose estrogen ameliorates experimental autoimmune encephalomyelitis in ovariectomized mice

Haghmorad

Salehipour

Nosratabadi

et al. 2016

Journal of Immunotoxicology

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Estrogen is a neuro-protective hormone in various central nervous system (CNS) disorders. The present study evaluated the role of estrogen during experimental autoimmune encephalomyelitis (EAE) at doses selected to mimic any suppressive potential from the hormone during pregnancy. Here, mice were ovariectomized and then 2 weeks later treated with MOG antigen to induce EAE. Concurrently, mice then received (subcutaneously) an implanted pellet to deliver varying estrogen amounts over a 21-day period. Clinical scores and other parameters were monitored daily for the 21 days. At the end of the period, brain/spinal cord histology was performed to measure lymphocyte infiltration; T-cell profiles were determined through ELISA, flow cytometry, and real-time PCR. Transcription factor expression levels in the CNS were assessed using real-time PCR; T-cell differentiation was evaluated via flow cytometry. The results demonstrated that estrogen inhibited development of EAE. Histological studies revealed limited leukocyte infiltration into the CNS. High and medium dose of estrogen increased T H 2 and T reg cell production of interleukin (IL)-4, IL-10, and transforming growth factor (TGF)-b, but concurrently resulted in a significant reduction in production of interferon (IFN)-c, IL-17, and IL-6. Flow cytometry revealed there were also significant decreases in the percentages of T H 1 and T H 17 cells, as well as significant increase in percentages of T reg and T H 2 cells in the spleen and lymph nodes. Real-time PCR results indicated that high-and medium-dose estrogen treatments reduced T-bet and ROR-ct factor expression, but enhanced Foxp3 and GATA3 expression. Collectively, these results demonstrated that a medium dose of estrogen -similar to a pregnancy level of estrogen -could potentially reduce the incidence and severity of autoimmune EAE and possibly other autoimmune pathologies.ARTICLE HISTORY

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Section: Introductionmentioning

confidence: 77%

Medium-dose estrogen ameliorates experimental autoimmune encephalomyelitis in ovariectomized mice

Haghmorad

Salehipour

Nosratabadi

et al. 2016

Journal of Immunotoxicology

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“…Lacto-N-fucopentaose III (LNFPIII), a glycan component of SEA, has been shown to act directly on DC and monocytes to favor the development of the T H 2 response (Wang et al, 2010; Zhu et al, 2012). In comparison to LPS stimulation, LNFPIII induced an increase in the ratio of CD86/CD80 expression on DC, a similar pattern of chemokine expression, higher expression of IL-6 but no IL-12 from purified DC (Wang et al, 2010).…”

Section: Schistosome Granuloma Formation As a Dynamic Model Of Adaptimentioning

confidence: 99%

“…LNFPIII was also shown to program macrophages to induce IFNγ production from NK cells by an IL-12-independent, but CD40/CD40L-dependent mechanism. Treatment with dextran conjugated to LNFPIII was successful at inhibiting experimental autoimmune encephalomyelitis (EAE) in mice through a mechanism involving alternative activation of CD11b + Ly-6C high monocytes (Zhu et al, 2012). The LNFPIII-treated TCR transgenic 2D2 mice had elevated levels of IFNγ as well as IL-4, IL-5, IL-13, and IL-10 in response to immunization with MOG peptide in comparison with mice that received unconjugated protein (Zhu et al, 2012).…”

Section: Schistosome Granuloma Formation As a Dynamic Model Of Adaptimentioning

confidence: 99%

“…Treatment with dextran conjugated to LNFPIII was successful at inhibiting experimental autoimmune encephalomyelitis (EAE) in mice through a mechanism involving alternative activation of CD11b + Ly-6C high monocytes (Zhu et al, 2012). The LNFPIII-treated TCR transgenic 2D2 mice had elevated levels of IFNγ as well as IL-4, IL-5, IL-13, and IL-10 in response to immunization with MOG peptide in comparison with mice that received unconjugated protein (Zhu et al, 2012). These data demonstrate alternate pathways by which LNFPIII elicits both IFNγ production from NK and CTL cells while also mediating a T H 2 and T REG dominated responses from CD4 + T cells, and suggest a mechanism for the induction of T H 2 cells in the face of a strong T H 1 immune response.…”

Section: Schistosome Granuloma Formation As a Dynamic Model Of Adaptimentioning

confidence: 99%

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Chronic schistosome infection leads to modulation of granuloma formation and systemic immune suppression

Lundy¹,

Lukacs²

2013

Front. Immun.

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Schistosome worms have been infecting humans for millennia, but it is only in the last half century that we have begun to understand the complexities of this inter-relationship. As our sophistication about the inner workings of every aspect of the immune system has increased, it has also become obvious that schistosome infections have broad ranging effects on nearly all of the innate and adaptive immune response mechanisms. Selective pressures on both the worms and their hosts, has no doubt led to co-evolution of protective mechanisms, particularly those that favor granuloma formation around schistosome eggs and immune suppression during chronic infection. The immune modulatory effects that chronic schistosome infection and egg deposition elicit have been intensely studied, not only because of their major implications to public health issues, but also due to the emerging evidence that schistosome infection may protect humans from severe allergies and autoimmunity. Mouse models of schistosome infection have been extremely valuable for studying immune modulation and regulation, and in the discovery of novel aspects of immunity. A progression of immune reactions occurs during granuloma formation ranging from innate inflammation, to activation of each branch of adaptive immune response, and culminating in systemic immune suppression and granuloma fibrosis. Although molecular factors from schistosome eggs have been identified as mediators of immune modulation and suppressive functions of T and B cells, much work is still needed to define the mechanisms of the immune alteration and determine whether therapies for asthma or autoimmunity could be developed from these pathways.

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“…It is noteworthy that in this study, we did not use pretreatment or even cotreatment in the first evaluation of MSc1 in animals with EAE. 30,31 Our purpose was to design a therapeutic study, beginning our therapy 14 days after disease induction, when paralysis symptoms were observed among the samples. The graph of clinical scores of the animal models showed that on the peak day of EAE, which is usually between 20 and 30 days after disease induction, MSc1 had efficiently slowed the progression of the disease in comparison to the control group and reduced the clinical score in favor of curing the diseased mice in a dose-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

The therapeutic effects of MSc1 nanocomplex, synthesized by nanochelating technology, on experimental autoimmune encephalomyelitic C57/BL6 mice

Fakharzadeh¹,

Sahraian²,

Hafizi³

et al. 2014

IJN

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Purpose Currently approved therapies for multiple sclerosis (MS) at best only slow down its progression. Therefore, it is necessary to utilize novel technologies in order to synthesize smart multifunctional structures. In the present study, for the first time we evaluated the therapeutic potential of MSc1 nanocomplex, which was designed based on novel nanochelating technology. Materials and methods MSc1 cell-protection capacity, with and without iron bond, was evaluated against hydrogen peroxide (H 2 O 2 )-induced oxidative stress in cultured rat pheochromocytoma-12 cells. The ability of MSc1 to maintain iron bond at pH ranges of 1–7 was evaluated. Nanocomplex toxicity was examined by estimating the intraperitoneal median lethal dose (LD 50 ). Experimental autoimmune encephalomyelitic mice were injected with MSc1 14 days after disease induction, when the clinical symptoms appeared. The clinical score, body weight, and disease-induced mortality were monitored until day 54. In the end, after collecting blood samples for assessing hemoglobin and red blood cell count, the brains and livers of the mice were isolated for hematoxylin and eosin staining and analysis of iron content, respectively. Results The results showed that MSc1 prevented H 2 O 2 -induced cell death even after binding with iron, and it preserved its bond with iron constant at pH ranges 1–7. The nanocomplex intraperitoneal LD 50 was 1,776.59 mg/kg. MSc1 prompted therapeutic behavior and improved the disabling features of experimental autoimmune encephalomyelitis, which was confirmed by decreased clinical scores versus increased body mass and 100% survival probability. It did not cause any adverse effects on hemoglobin or red blood cell count. Histopathological studies showed no neural loss or lymphocyte infiltration in MSc1-treated mice, while the hepatic iron content was also normal. Conclusion These results demonstrate that MSc1 could be a promising beneficial novel agent and has the capacity to be evaluated in further studies.

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Immune modulation by Lacto-N-fucopentaose III in experimental autoimmune encephalomyelitis

Cited by 50 publications

References 46 publications

Medium-dose estrogen ameliorates experimental autoimmune encephalomyelitis in ovariectomized mice

Medium-dose estrogen ameliorates experimental autoimmune encephalomyelitis in ovariectomized mice

Chronic schistosome infection leads to modulation of granuloma formation and systemic immune suppression

The therapeutic effects of MSc1 nanocomplex, synthesized by nanochelating technology, on experimental autoimmune encephalomyelitic C57/BL6 mice

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