The inhibitory role of γ-aminobutyric acid (GABA) on immunomodulation of Pacific oyster Crassostrea gigas

• Neurotransmitter GABA was identified in hemolymph of oyster.
• The GABA in hemolymph increased at late phase of immune response against LPS stimulation.
• GABA could inhibit the expression of cytokines and immune effectors on mRNA level.
• GABA could suppress the activity of NOS on protein level.
• GABA exhibited inhibitory role on hemocytes phagocytosis and apoptosis of oyster.

γ-aminobutyric acid (GABA) is an inhibitory neurotransmitter to suppress the immune-mediated pro-inflammatory reactions, and it has been used in the treatment of many inflammation-related diseases in vertebrates, while its immunomodulatory role in invertebrates has never been reported. In the present study, GABA was found to exist in the hemolymph of Pacific oyster Crassostrea gigas, and its concentration decreased slightly from 8.00 ± 0.37 μmol L−1 at normal condition to 7.73 ± 0.15 μmol L−1 at 6 h after LPS stimulation, and then increased to 9.34 ± 0.15 μmol L−1, 8.86 ± 0.68 μmol L−1 at 12 h and 48 h, respectively. After LPS stimulation, the mRNA expressions of pro-inflammatory cytokines (CgIL-17 and CgTNF) and immune effectors (CgSOD and CgBPI), and the protein expression of NOS increased significantly, and these increased trends were remarkably inhibited by GABA stimulation. At the same time, the phagocytosis rate and apoptosis rate of immunocytes also increased obviously after LPS stimulation, whereas the increase was repressed with the addition of GABA. The results collectively demonstrated that GABA was an indispensable inhibitory agent for both humoral and cellular immune response, which mainly functioned at the late phase of immune response to avoid the excess immune reactions and maintain the immune homeostasis.