## 4 Discussion  
We are exposed to a variety of pathogens during our lifespan. Of those, a small number of pathogens manage to cause disease by impairing the immune system. The innate immune system provides the first line of defense against these pathogens [51; 52]. Different innate immune cells such as monocytes, macrophages, and dendritic cells come into direct contact with these pathogens and trigger a series of reactions to fight against them. Macrophages scavenge and dispose of pathogens. They implement multiple and complex signaling pathways to deal with infectious pathogens by expressing pattern recognition receptors [53], which recognize unique conserved molecular patterns of pathogen surfaces and produce various cytokines such as TNF-\(\alpha\), IL-1\(\beta\), IL-6, and IL-12. This initiates inflammation and the phagocytosis of the pathogen [54]. Recent studies have reported various immunomodulators that regulate macrophage function and target various chronic diseases. Natural or plant-derived immunomodulators are considered a promising approach in modulating macrophage function while dealing with different pathogens or chronic diseases, because they contain bioactive compounds [14; 15; 16]. Brown algae contain a common sulfated polysaccharide, fucoidan, which has been studied in various diseases for its potentially bioactive properties, such as antiviral, anticancer, and anti-inflammatory properties attributed to molecular weights and sulfate contents [42; 43; 44; 45]. _Sargassum horneri_ has also been recognized as an environmental pollutant, particularly on Jeju Island, Korea [55]. Fish farms were found to be polluted with it, and an unpleasant odor on the beaches could be observed owing to its presence [56], which is regarded as an economic burden [57]. Thus, the Korean government and researchers are constantly contributing to efforts to use these materials as beneficial materials [58; 59]. Previous studies have supported the beneficial role of _Sargassum_ sp. as anti-inflammatory [60; 61], anticancer [62], antioxidant [63], and immunoenhancing agents [64]. On the other hand, _Undaria pinnatifida_ is found in Asian countries (such as Korea, Japan, and China), as well as in Australia and European countries. They are considered a popular seaweed that has been used as food in Asian regions for a longer period [65]. Sporophyll, a byproduct of _U. pinnatifida_, contains more polysaccharides than its edible portion. _U. pinnatifida_ possesses various bioactivities, including anti-inflammatory [66], antioxidant [67], and antitumor [68] properties. In our study, we focused on evaluating the immunomodulatory roles of the extracts of brown algae, such as _S. horneri_, _S. fusiforme_, and _U. pinnatifida_. We found that none of these extracts were harmful or caused any toxicity to RAW 264.7 cells when exposed for 24 h.  
Cytokines and chemokines released by macrophages as a host defense mechanism play crucial roles in immune impairment. The IL-1\(\beta\), IL-6, TNF-\(\alpha\), and IL-12 have been reported to be involved in providing innate and adaptive immunity [69]. [PERSON] et al. described the immune-enhancing effects of SH by increasing IL-1\(\beta\), IL-6, and TNF-\(\alpha\) expression in immunosuppressed mice and primary cultured splenocytes [70]. Additionally, [PERSON] et al. analyzed the effect of a novel polysaccharide, UPP-2, from UP and observed its immune-enhancing effects on RAW264.7 cells [71]. Also, the immune-enhancing effects of SH on immunosuppressed BALB/c mice and cultured primary splenocytes were reported [70]. Our study followed in the footsteps of the previous findings, and we found that all three algal extracts were able to affect the mRNA expression levels of IL-1\(\beta\), TNF-\(\alpha\), and IL-6 and the protein expression levels of TNF-\(\alpha\) and IL-6, as shown in a previous study on fucoidan extracted from _Laminaria_ in THP-1 cells [72]. In addition, SH and SF showed upregulation in IL-12 mRNA expression. Only SH was able to upregulate the mRNA expression level of IL-10.