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. 2022 Jul 29;11(15):2340.
doi: 10.3390/cells11152340.

A Comparative Analysis of Mucus Immunomodulatory Properties from Seven Marine Gastropods from the Mediterranean Sea

Affiliations

A Comparative Analysis of Mucus Immunomodulatory Properties from Seven Marine Gastropods from the Mediterranean Sea

Clementina Sansone et al. Cells. .

Abstract

The treatment of inflammatory and immune-related diseases due to dysfunctioning of the immune system necessitates modulation of the immune response through immunomodulatory compounds. Marine environments are considered as a new frontier for health benefit product implementations. Marine biodiversity is still a low explored resource, despite it is expected to represent an important platform for chemical bioactive compounds. Within the phylum Mollusca, gastropods are known to synthetize mucus, the latter presenting relevant bioactive properties, e.g., related to immunomodulant molecules able to activate the innate and acquired immune system. This study proposes a bioprospecting of the immunomodulant activity of mucus isolated from seven common gastropod species from the Gulf of Naples (Mediterranean Sea). Results showed that not all mucus displayed a significant cytotoxic activity on the two human cancer cell lines A549 and A2058. On the other hand, the mucus from Bolinus brandaris was strongly bioactive and was therefore thoroughly investigated at cellular, molecular, and protein levels on the human monocytes U937 line. It can conclusively induce monocyte differentiation in vitro and significantly stimulate natural immunity response.

Keywords: gastropods’ mucus; immunomodulation; marine biotechnology; monocytes’ differentiation.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Percentage of human cell lines treated during 48 h with 1, 10 or 100 µg mL−1 of lyophilized mucus extracted or isolated from marine gastropods. Panels (AC) represent results obtained by MTT assay on A549, A2058, and normal monocyte cell lines (U937) treated with lyophilized mucus. Statistical significance is calculated through Dunnett test and is indicated by **** (p ≤ 0.0001), *** (p ≤ 0.0005), ** (p ≤ 0.005), and * (p ≤ 0.05). Values are expressed as mean ± standard deviation.
Figure 2
Figure 2
Flow cytometry analysis U937 incubated with Bolinus brandaris mucus (Bbm). The combination of FSC (proportional to cell-surface area or size) and SSC (proportional to morphology, cell granularity, or internal complexity) was used to discriminate human monocyte population P1 (in red) in all the dot plot. In (A), it is represented the control (untreated cells). (B) represented cells incubated with 100 µg mL−1 of Bbm respectively. P2–P9 indicate the changes in morphology and size of the monocyte population when in contact with the highest Bbm concentration.
Figure 3
Figure 3
Fold regulation (with respect to the untreated U937 cells) of 27 genes implicated in inflammatory response in U937 cells treated with Bbm.
Figure 4
Figure 4
The effect of Bbm on serum-released interleukin 6 (IL-6) in human monocytic cells (U937). Values are expressed as average of IL-6 concentration (ng mL−1) determined by ELISA in culture medium of cells treated with 10 μg mL−1 of Bbm and untreated cells (Control) for 24 h. n = 3; * p ≤ 0.05 (Student’s t-test analysis).
Figure 5
Figure 5
(A) Human inflammation array analysis of the conditional medium from U937 cells treated with 10 μg mL−1 of Bolinus brandaris mucus (Bbm). (B) Relative expression levels of the four inflammation cytokines, IL-8, MIP-1β, sTNF-RII and TIMP-2. Statistical significance is calculated through Sidak’s test and is indicated by **** (p ≤ 0.0001), *** (p ≤ 0.0005), ** (p ≤ 0.005). Values are expressed as mean ± standard deviation.

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