Agarum clathratum (A. clathratum) is a marine brown algal species that belongs to the Costariaceae family and has antioxidant and anti-microbial properties. However, the anti-inflammatory effects of A. clathratum and the molecular mechanisms involved have not been determined so far. This study aimed to investigate the anti-inflammatory effects of A. clathratum extracts in THP-1 macrophages stimulated by lipopolysaccharide (LPS) derived from Porphyromonas gingivalis. The THP-1 cells were differentiated with 12-O-tetradecanoylphorbol-13-acetate and treated with A. clathratum before LPS stimulation. Cell viability was assessed using the trypan blue exclusion assay. The expression of pro-inflammatory response-associated molecules was evaluated by quantitative real-time polymerase chain reaction and Western blot analysis. A. clathratum treatment inhibited the expression of interleukin-1β in LPS-stimulated THP-1 macrophages without causing any cytotoxicity. The anti-inflammatory effect of A. clathratum resulted in a significant repression of the JNK/c-Jun signaling axis, a key regulator in inflammation responses. This study highlights the possible role of A. clathratum in the inhibition of pro-inflammatory cytokines via suppression of the JNK/c-Jun signaling axis and suggests that A. clathratum could serve as a marine-derived anti-inflammatory agent in periodontitis.

Substantia gelatinosa (SG) neurons receive synaptic inputs from primary afferent Aδ- and C-fibers, where nociceptive information is integrated and modulated by numerous neurotransmitters or neuromodulators. A number of studies were dedicated to the molecular mechanism underlying the modulation of excitability or synaptic plasticity in SG neurons and revealed that second messengers, such as cAMP and cGMP, play an important role. Recently, cAMP and cGMP were shown to downregulate each other in heart muscle cells. However, involvement of the crosstalk between cAMP and cGMP in neurons is yet to be addressed. Therefore, we investigated whether interaction between cAMP and cGMP modulates synaptic plasticity in SG neurons using slice patchclamp recording from rats. Synaptic activity was measured by excitatory post-synaptic currents (EPSCs) elicited by stimulation onto dorsal root entry zone. Application of 1 mM of 8- bromoadenosine 3,5-cyclic monophosphate (8-Br-cAMP) or 8-bromoguanosine 3,5-cyclic monophosphate (8-Br-cGMP) for 15 minutes increased EPSCs, which were maintained for 30 minutes. However, simultaneous application of 8-BrcAMP and 8-Br-cGMP failed to increase EPSCs, which suggested antagonistic cross-talk between two second messengers. Application of 3-isobutyl-1-methylxanthine (IBMX) that prevents degradation of cAMP and cGMP by blocking phosphodiesterase (PDE) increased EPSCs. Co-application of cAMP/cGMP along with IBMX induced additional increase in EPSCs. These results suggest that second messengers, cAMP and cGMP, might contribute to development of chronic pain through the mutual regulation of the signal transduction.

The role of Cl channels in regulatory volume decrease (RVD) in human salivary gland acinar cells was examined using a whole-cell patch clamp technique. Human tissues were obtained from healthy volunteers or from patients with oromaxillofacial tumors. During the measurements, K+-free solutions were employed to eliminate contamination of whole-cell conductance by K+ currents. When the cells were exposed to a 70% hypotonic solution, outward-rectifying currents, which were not observed in the resting state, were found to have significantly increased both in human labial and parotid gland acinar cells. The amplitudes of the currents were reduced in a low CI bath solution. Furthermore, the addition of 100μM 5-Nitro-2- (3-phenyl propylamino) benzoic acid (NPPB) or 100μM 4,4'-diisothio cyanatostilbene-2,2'-disulphonic acid (DIDS), known to partially block Cl channels, significantly inhibited these currents. Its outward-rectifying current profile, shift in reversal potential in a low Cl bath solution and pharmacological properties suggest that this is a Cα2+ independent, volume activated Cl current. We conclude therefore that volume activated Cl channels play a putative role in RVD in human salivary gland acinar cells.