Fermented Lettuce Extract Induces Immune Responses through Polarization of Macrophages into the Pro-Inflammatory M1-Subtype

It has been reported that lettuce and its bioactive compounds enhance the host immune system by acting as immune modulators. This study aimed to identify the immunological effect of fermented lettuce extract (FLE) on macrophages. To evaluate the efficacy of FLE in enhancing macrophage function, we m...

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Main Authors: Bo-Young Kim, Ji Hyeon Ryu, Jisu Park, Byeongjun Ji, Hyun Soo Chun, Min Sun Kim, Yong-Il Shin
Format: Article
Language:English
Published: MDPI AG 2023-06-01
Series:Nutrients
Subjects:
Online Access:https://www.mdpi.com/2072-6643/15/12/2750
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author Bo-Young Kim
Ji Hyeon Ryu
Jisu Park
Byeongjun Ji
Hyun Soo Chun
Min Sun Kim
Yong-Il Shin
author_facet Bo-Young Kim
Ji Hyeon Ryu
Jisu Park
Byeongjun Ji
Hyun Soo Chun
Min Sun Kim
Yong-Il Shin
author_sort Bo-Young Kim
collection DOAJ
description It has been reported that lettuce and its bioactive compounds enhance the host immune system by acting as immune modulators. This study aimed to identify the immunological effect of fermented lettuce extract (FLE) on macrophages. To evaluate the efficacy of FLE in enhancing macrophage function, we measured and compared the levels of macrophage activation-related markers in FLE- and lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Treatment with FLE activated RAW 264.7 macrophages, increased their phagocytic ability, and increased the production of nitric oxide (NO) and pro-inflammatory cytokine levels—similar to LPS. The effects of FLE on M1/M2 macrophage polarization were investigated by determining M1 and M2 macrophage transcript markers in mouse peritoneal macrophages. The FLE-related treatment of peritoneal macrophages enhanced the expression of M1 markers but reduced IL-4 treatment-induced M2 markers. After the generation of tumor-associated macrophages (TAMs), alterations in the levels of M1 and M2 macrophage markers were measured after treatment with FLE. The FLE-related treatment of TAMs increased the expression and production of pro-inflammatory cytokines and also led to the enhanced apoptosis of pancreatic cancer cells. These findings suggest that FLE may be useful for macrophage-targeted cancer therapy because of its ability to regulate the activation and polarization of macrophages in the tumor microenvironment.
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spelling doaj.art-8f2950e789914931a75a7b4da044089e2023-11-18T11:57:04ZengMDPI AGNutrients2072-66432023-06-011512275010.3390/nu15122750Fermented Lettuce Extract Induces Immune Responses through Polarization of Macrophages into the Pro-Inflammatory M1-SubtypeBo-Young Kim0Ji Hyeon Ryu1Jisu Park2Byeongjun Ji3Hyun Soo Chun4Min Sun Kim5Yong-Il Shin6Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of KoreaResearch Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of KoreaResearch Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of KoreaHumanEnos LLC, Wanju 55347, Republic of KoreaHumanEnos LLC, Wanju 55347, Republic of KoreaCenter for Nitric Oxide Metabolite, Wonkwang University, Iksan 54538, Republic of KoreaResearch Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of KoreaIt has been reported that lettuce and its bioactive compounds enhance the host immune system by acting as immune modulators. This study aimed to identify the immunological effect of fermented lettuce extract (FLE) on macrophages. To evaluate the efficacy of FLE in enhancing macrophage function, we measured and compared the levels of macrophage activation-related markers in FLE- and lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Treatment with FLE activated RAW 264.7 macrophages, increased their phagocytic ability, and increased the production of nitric oxide (NO) and pro-inflammatory cytokine levels—similar to LPS. The effects of FLE on M1/M2 macrophage polarization were investigated by determining M1 and M2 macrophage transcript markers in mouse peritoneal macrophages. The FLE-related treatment of peritoneal macrophages enhanced the expression of M1 markers but reduced IL-4 treatment-induced M2 markers. After the generation of tumor-associated macrophages (TAMs), alterations in the levels of M1 and M2 macrophage markers were measured after treatment with FLE. The FLE-related treatment of TAMs increased the expression and production of pro-inflammatory cytokines and also led to the enhanced apoptosis of pancreatic cancer cells. These findings suggest that FLE may be useful for macrophage-targeted cancer therapy because of its ability to regulate the activation and polarization of macrophages in the tumor microenvironment.https://www.mdpi.com/2072-6643/15/12/2750lettuceM1/M2 macrophagestumor-associated macrophages
spellingShingle Bo-Young Kim
Ji Hyeon Ryu
Jisu Park
Byeongjun Ji
Hyun Soo Chun
Min Sun Kim
Yong-Il Shin
Fermented Lettuce Extract Induces Immune Responses through Polarization of Macrophages into the Pro-Inflammatory M1-Subtype
Nutrients
lettuce
M1/M2 macrophages
tumor-associated macrophages
title Fermented Lettuce Extract Induces Immune Responses through Polarization of Macrophages into the Pro-Inflammatory M1-Subtype
title_full Fermented Lettuce Extract Induces Immune Responses through Polarization of Macrophages into the Pro-Inflammatory M1-Subtype
title_fullStr Fermented Lettuce Extract Induces Immune Responses through Polarization of Macrophages into the Pro-Inflammatory M1-Subtype
title_full_unstemmed Fermented Lettuce Extract Induces Immune Responses through Polarization of Macrophages into the Pro-Inflammatory M1-Subtype
title_short Fermented Lettuce Extract Induces Immune Responses through Polarization of Macrophages into the Pro-Inflammatory M1-Subtype
title_sort fermented lettuce extract induces immune responses through polarization of macrophages into the pro inflammatory m1 subtype
topic lettuce
M1/M2 macrophages
tumor-associated macrophages
url https://www.mdpi.com/2072-6643/15/12/2750
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