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Herbal preparation (HemoHIM) enhanced functional maturation of bone marrow-derived dendritic cells mediated toll-like receptor 4.

Lee SJ, Kim JJ, Kang KY, Hwang YH, Jeong GY, Jo SK, Jung U, Park HR, Yee ST - BMC Complement Altern Med (2016)

Bottom Line: HemoHIM, which is an herbal preparation of three edible herbs (Angelicam gigas Nakai, Cnidium offinale Makino, and Peaonia japonica Miyabe), is known to have various biological and immunological activities, but the modulatory effects of this preparation on dendritic cells (DCs)-mediated immune responses have not been examined previously.Furthermore, the antigen-uptake ability of BMDCs was decreased by HemoHIM, and the antigen-presenting ability of HemoHIM-treated mature BMDCs increased TLR4-dependent CD4(+) and CD8(+) T cell responses.These results suggest that HemoHIM has the potential to mediate DC immune responses.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Sunchon National University, 255 Joongang-Ro, Seokhyeon-Dong, Suncheon, 549-742, Republic of Korea. 6525140@hanmail.net.

ABSTRACT

Background: HemoHIM, which is an herbal preparation of three edible herbs (Angelicam gigas Nakai, Cnidium offinale Makino, and Peaonia japonica Miyabe), is known to have various biological and immunological activities, but the modulatory effects of this preparation on dendritic cells (DCs)-mediated immune responses have not been examined previously. DCs are a unique group of white blood cells that initiate primary immune responses by capturing, processing, and presenting antigens to T cells.

Results: In the present study, we investigated the effect of HemoHIM on the functional and phenotypic maturation of murine bone marrow-derived dendritic cells (BMDCs) both in vitro and in vivo. The expression of co-stimulatory molecules (CD40, CD80, CD86, MHC I, and MHC II) and the production of cytokines (IL-1β, IL-6, IL-12p70, and TNF-α) were increased by HemoHIM in BMDCs. Furthermore, the antigen-uptake ability of BMDCs was decreased by HemoHIM, and the antigen-presenting ability of HemoHIM-treated mature BMDCs increased TLR4-dependent CD4(+) and CD8(+) T cell responses.

Conclusions: Our findings demonstrated that HemoHIM induces TLR4-mediated BMDCs functional and phenotypic maturation through in vivo and in vitro. And our study showed the antigen-presenting ability that HemoHIM-treated mature BMDCs increase CD4(+) and CD8(+) T cell responses by in vitro. These results suggest that HemoHIM has the potential to mediate DC immune responses.

No MeSH data available.


Related in: MedlinePlus

HemoHIM bound TLR4 but not TLR2 and induced BMDC activation. a Histograms of CD40, CD80, CD86, and MHC II expression by HemoHIM treated (100 μg/ml) CD11c-gated DCs derived from wild-type, TLR2-/-, or TLR4-/- mice. DCs derived from wild-type, TLR2-/- and TLR4-/- mice were treated with HemoHIM for 24 h. The percentages of positive cells are shown in each panel. b IL-1β, IL-6, and TNF-α production by HemoHIM-, LPS-, or Pam3-treated DCs derived from wild-type, TLR2-/-, or TLR4-/- mice were determined by ELISA. The results are representative of three experiments. *, p < 0.05, **, p < 0.01, and ***, p < 0.001 vs. untreated BMDCs. +, p < 0.05, ++, p < 0.01, and +++, p < 0.001 vs. HemoHIM-treated BMDCs from wild-type and TLR2-/- mice
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Fig7: HemoHIM bound TLR4 but not TLR2 and induced BMDC activation. a Histograms of CD40, CD80, CD86, and MHC II expression by HemoHIM treated (100 μg/ml) CD11c-gated DCs derived from wild-type, TLR2-/-, or TLR4-/- mice. DCs derived from wild-type, TLR2-/- and TLR4-/- mice were treated with HemoHIM for 24 h. The percentages of positive cells are shown in each panel. b IL-1β, IL-6, and TNF-α production by HemoHIM-, LPS-, or Pam3-treated DCs derived from wild-type, TLR2-/-, or TLR4-/- mice were determined by ELISA. The results are representative of three experiments. *, p < 0.05, **, p < 0.01, and ***, p < 0.001 vs. untreated BMDCs. +, p < 0.05, ++, p < 0.01, and +++, p < 0.001 vs. HemoHIM-treated BMDCs from wild-type and TLR2-/- mice

Mentions: Associations between activated DCs and TLRs are critical for the tailoring of immune responses. We investigated whether TLRs on BMDCs recognized HemoHIM using TLR2-/- and TLR4-/- mice. To confirm that TLRs on BMDCs interact with HemoHIM, wild-type, TLR2-/-, or TLR4-/- BMDCs were stimulated with HemoHIM for 24 h. Pam3 (a TLR2 agonist) and LPS (a TLR4 agonist) were used as positive controls. After stimulation for 24 h, we measured the expressions of the BMDCs maturation markers CD40, CD80, CD86, and MHC II and of various cytokines (i.e., IL-1β, IL-6, and TNF-α). As shown in Fig. 7a, untreated BMDCs from wild-type, TLR2-/-, and TLR4-/- mice expressed similar levels of these markers and cytokines. However, HemoHIM-treated BMDCs from wild-type and TLR2-/- mice exhibited higher expression of the investigated surface maturation markers than untreated wild-type or TLR2-/- BMDCs [wild-type: CD40 (24.4 %), CD80 (75.5 %), CD86 (76.1 %), and MHC II (75.7 %); and TLR2-/- : CD40 (28.5 %), CD80 (78.3 %), CD86 (74.6 %), and MHC II (67.6 %)]. In contrast, these effects were diminished in BMDCs from TLR4-/-mice, indicating that HemoHIM is an agonist of TLR4 in BMDCs [TLR4-/- : CD40 (14.4 %) and CD80 (67.9 %)]. In contrast, the expression levels of CD80 and CD86 were significantly more reduced by HemoHIM in BMDCs from TLR4-/- mice than in BMDCs from wild-type or TLR2-/- mice [wild-type: CD80 (75.5 %) and CD86 (76.1 %); TLR2-/- : CD80 (78.3 %) and CD86 (74.6 %); and TLR4-/- : CD80 (67.9 %) and CD86 (67.8 %)]. In addition, cytokine production exhibited a pattern similar to that observed for surface molecules (Fig. 7b). These results demonstrate that HemoHIM induces TLR4-mediated BMDC maturation.Fig. 7


Herbal preparation (HemoHIM) enhanced functional maturation of bone marrow-derived dendritic cells mediated toll-like receptor 4.

Lee SJ, Kim JJ, Kang KY, Hwang YH, Jeong GY, Jo SK, Jung U, Park HR, Yee ST - BMC Complement Altern Med (2016)

HemoHIM bound TLR4 but not TLR2 and induced BMDC activation. a Histograms of CD40, CD80, CD86, and MHC II expression by HemoHIM treated (100 μg/ml) CD11c-gated DCs derived from wild-type, TLR2-/-, or TLR4-/- mice. DCs derived from wild-type, TLR2-/- and TLR4-/- mice were treated with HemoHIM for 24 h. The percentages of positive cells are shown in each panel. b IL-1β, IL-6, and TNF-α production by HemoHIM-, LPS-, or Pam3-treated DCs derived from wild-type, TLR2-/-, or TLR4-/- mice were determined by ELISA. The results are representative of three experiments. *, p < 0.05, **, p < 0.01, and ***, p < 0.001 vs. untreated BMDCs. +, p < 0.05, ++, p < 0.01, and +++, p < 0.001 vs. HemoHIM-treated BMDCs from wild-type and TLR2-/- mice
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Fig7: HemoHIM bound TLR4 but not TLR2 and induced BMDC activation. a Histograms of CD40, CD80, CD86, and MHC II expression by HemoHIM treated (100 μg/ml) CD11c-gated DCs derived from wild-type, TLR2-/-, or TLR4-/- mice. DCs derived from wild-type, TLR2-/- and TLR4-/- mice were treated with HemoHIM for 24 h. The percentages of positive cells are shown in each panel. b IL-1β, IL-6, and TNF-α production by HemoHIM-, LPS-, or Pam3-treated DCs derived from wild-type, TLR2-/-, or TLR4-/- mice were determined by ELISA. The results are representative of three experiments. *, p < 0.05, **, p < 0.01, and ***, p < 0.001 vs. untreated BMDCs. +, p < 0.05, ++, p < 0.01, and +++, p < 0.001 vs. HemoHIM-treated BMDCs from wild-type and TLR2-/- mice
Mentions: Associations between activated DCs and TLRs are critical for the tailoring of immune responses. We investigated whether TLRs on BMDCs recognized HemoHIM using TLR2-/- and TLR4-/- mice. To confirm that TLRs on BMDCs interact with HemoHIM, wild-type, TLR2-/-, or TLR4-/- BMDCs were stimulated with HemoHIM for 24 h. Pam3 (a TLR2 agonist) and LPS (a TLR4 agonist) were used as positive controls. After stimulation for 24 h, we measured the expressions of the BMDCs maturation markers CD40, CD80, CD86, and MHC II and of various cytokines (i.e., IL-1β, IL-6, and TNF-α). As shown in Fig. 7a, untreated BMDCs from wild-type, TLR2-/-, and TLR4-/- mice expressed similar levels of these markers and cytokines. However, HemoHIM-treated BMDCs from wild-type and TLR2-/- mice exhibited higher expression of the investigated surface maturation markers than untreated wild-type or TLR2-/- BMDCs [wild-type: CD40 (24.4 %), CD80 (75.5 %), CD86 (76.1 %), and MHC II (75.7 %); and TLR2-/- : CD40 (28.5 %), CD80 (78.3 %), CD86 (74.6 %), and MHC II (67.6 %)]. In contrast, these effects were diminished in BMDCs from TLR4-/-mice, indicating that HemoHIM is an agonist of TLR4 in BMDCs [TLR4-/- : CD40 (14.4 %) and CD80 (67.9 %)]. In contrast, the expression levels of CD80 and CD86 were significantly more reduced by HemoHIM in BMDCs from TLR4-/- mice than in BMDCs from wild-type or TLR2-/- mice [wild-type: CD80 (75.5 %) and CD86 (76.1 %); TLR2-/- : CD80 (78.3 %) and CD86 (74.6 %); and TLR4-/- : CD80 (67.9 %) and CD86 (67.8 %)]. In addition, cytokine production exhibited a pattern similar to that observed for surface molecules (Fig. 7b). These results demonstrate that HemoHIM induces TLR4-mediated BMDC maturation.Fig. 7

Bottom Line: HemoHIM, which is an herbal preparation of three edible herbs (Angelicam gigas Nakai, Cnidium offinale Makino, and Peaonia japonica Miyabe), is known to have various biological and immunological activities, but the modulatory effects of this preparation on dendritic cells (DCs)-mediated immune responses have not been examined previously.Furthermore, the antigen-uptake ability of BMDCs was decreased by HemoHIM, and the antigen-presenting ability of HemoHIM-treated mature BMDCs increased TLR4-dependent CD4(+) and CD8(+) T cell responses.These results suggest that HemoHIM has the potential to mediate DC immune responses.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Sunchon National University, 255 Joongang-Ro, Seokhyeon-Dong, Suncheon, 549-742, Republic of Korea. 6525140@hanmail.net.

ABSTRACT

Background: HemoHIM, which is an herbal preparation of three edible herbs (Angelicam gigas Nakai, Cnidium offinale Makino, and Peaonia japonica Miyabe), is known to have various biological and immunological activities, but the modulatory effects of this preparation on dendritic cells (DCs)-mediated immune responses have not been examined previously. DCs are a unique group of white blood cells that initiate primary immune responses by capturing, processing, and presenting antigens to T cells.

Results: In the present study, we investigated the effect of HemoHIM on the functional and phenotypic maturation of murine bone marrow-derived dendritic cells (BMDCs) both in vitro and in vivo. The expression of co-stimulatory molecules (CD40, CD80, CD86, MHC I, and MHC II) and the production of cytokines (IL-1β, IL-6, IL-12p70, and TNF-α) were increased by HemoHIM in BMDCs. Furthermore, the antigen-uptake ability of BMDCs was decreased by HemoHIM, and the antigen-presenting ability of HemoHIM-treated mature BMDCs increased TLR4-dependent CD4(+) and CD8(+) T cell responses.

Conclusions: Our findings demonstrated that HemoHIM induces TLR4-mediated BMDCs functional and phenotypic maturation through in vivo and in vitro. And our study showed the antigen-presenting ability that HemoHIM-treated mature BMDCs increase CD4(+) and CD8(+) T cell responses by in vitro. These results suggest that HemoHIM has the potential to mediate DC immune responses.

No MeSH data available.


Related in: MedlinePlus